supporting info 23 05 2007 · leuven, celestijnenlaan 200f, b-3001 leuven bbioorganic laboratory,...
TRANSCRIPT
S1
SUPPORTING INFORMATION
Palladium-Catalyzed Copper(I)-Mediated Cross-Coupling of Arylboronic Acids
and 2(1H)-Pyrazinones Facilitated by Microwave Irradiation with Simultaneous
Cooling
Brajendra Kumar Singh,a,b Vaibhav Pravinchandra Mehta,a Virinder Singh Parmar,b and Erik Van der Eyckena,*
aLaboratory for Organic & Microwave-Assisted Chemistry, Department of Chemistry, University of
Leuven, Celestijnenlaan 200F, B-3001 Leuven bBioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi 110 007, India
* To whom correspondence should be addressed. E-mail: [email protected]
Table of Contents
General remarks – Page S2 Microwave Irradiation Experiments − Page S2 Representative experimental procedure for the cross-coupling reaction under conventional condition – Page S2 Representative experimental procedure for the cross-coupling reaction under Microwave Irradiation with Simultaneous Cooling at 35 °C – Page S2 Spectral data of compounds 3{1-12}, 3{14}, 3{16-21}, 3{23} and 3{26-34} – Pages S3 to S7 Copy of the 1H- and 13C Spectra – Pages S8 to S36
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General Remarks: 1H NMR spectra were recorded on a Bruker Avance 300 MHz and 400 MHz instruments, using CDCl3. The 1H and 13C
chemical shifts are reported in ppm relative to tetramethylsilane, using the residual solvent signal as an internal reference.
Mass spectra were recorded by using a Kratos MS50TC and a Kratos Mach III data system. The ion source temperature was
150-250 °C as required. High resolution EI-mass spectra were performed with a resolution of 10000. The low resolution
spectra were obtained with a HP5989A MS instrument. For thin layer chromatography, analytical TLC plates (Alugram SIL
G/UV254 and 70-230 mesh silicagel (E.M.Merck)) were used. The Pd(PPh3)4, CuTC and boronic acids were purchased from
Acros Organics (Janssen Pharmaceutical, Geel) and were used without further purification. All starting pyrazinones were
prepared according to a known litrature procedure.12 All the compounds were fully characterised by comparison of their
spectral data and melting points. Melting points of the compounds are uncorrected.
Microwave Irradiation Experiments: All microwave irradiation experiments were carried out in a dedicated CEM-Discover-CoolmateTM monomode microwave
apparatus (CEM Corporation P.O. Box 200 Matthews, NC 28106), operating at a frequency of 2.45 GHz with continuous
irradiation power from 0 to 300 W. The reactions were carried out in an open 10 mL double walled glass vial which was
cooled to 0 °C - 35 °C using a microwave transparent cooling liquid.11(b) The temperature of the cooling liquid was between
10 °C and 15 °C. Irradiation and cooling were started simultaneously, starting with the reaction mixture at rt. The temperature
was measured with a fiber-optic device inserted into the reaction vessel (a schematic representation of the set-up can be found
at http://cemsynthesis.com/.
General Procedure of Liebeskind cross-Couping of Pyrazinone 1 with Boronic Acids :
A) Liebeskind Condition: To a suspension of pyrazinone 1 (0.076 g, 0.21 mmol) in THF (3 mL) were added boronic
acid (0.63 mmol, 3 equiv), Pd(PPh3)4 (5 mol %) and CuTC (2.0 equiv). The reaction mixture was heated at 65 °C for
various time interval (Table 1). After completion of the reaction, the solvent was removed under reduced pressure
and the residue was purified by column chromatography [silica gel, n-hexane-CH2Cl2 (95:5)] to furnish the products
3{1}-3{5}.
B) Upon microwave irradiation with simultaneous cooling at 0 °C : To a suspension of pyrazinone 1 (0.076 g, 0.21
mmol) in THF (3 mL) were added boronic acid (0.63 mmol, 3 equiv), Pd(PPh3)4 (5 mol %) and CuTC (2.0 equiv).
The mixture was irradiated at 35 °C continuously at the maximum power of 300 W for 1 h. After completion of the
reaction, the solvent was removed under reduced pressure. The crude product was then absorbed on silica gel and
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the residue was purified by column chromatography over silica gel using n-Hexane/ CH2Cl2 (95:5) as the eluent, to
give the C-3-arylated pyrazinones 3{1}-3{34}.
5-chloro-3-(3-ethoxyphenyl)-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{1}). It was obtained as a yellow oil in 88 % yield.
1H NMR (400 MHz, CDCl3): � 7.99-7.95 (m, 2H), 7.34-7.25 (m, 3H), 7.14(s, 1H), 7.00-6.98 (m, 1H), 6.89-6.87 (d, 2H,
J=8.36 Hz), 5.03 (s, 2H), 4.11-4.06 (q, 2H, J = 6.9 Hz), 3.76 (s, 3H), 1.42-139 (t, 3H, J = 6.9 Hz). 13C NMR (100 MHz,
CDCl3): 160.13, 158.78, 154.50, 151.9, 136.19, 130.46, 129.18, 126.41, 125.32, 121.93, 117.70, 114.81, 114.72, 63.66,
55.44, 52.45, 14.92. HRMS (EI): calcd for C20H19O3N2Cl: 370.1084, found: 370.1071.
5-chloro-3-(3-trifluoromethylphenyl)-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{2}). It was obtained as a yellow solid
m.p. 107-108 °C in 83 % yield. 1H NMR (300 MHz, CDCl3): � 8.72 (s, 1H), 8.63-8.60 (m, 1H), 7.71-7.68 (m, 1H), 7.58-7.53
(m, 1H), 7.32-7.30 (d, 2H, J = 8.2Hz), 7.23 (s, 1H), 6.93-6.90 (d, 2H, J = 9.1 Hz), 5.08 (s, 2H), 3.8 (s, 3H). 13C NMR (100
MHz, CDCl3): 160.18, 154.25, 150.18, 135.50, 132.40, 121.97, 130.35, 129.03, 128.55, 126.98, 126.46, 126.08, 114.72,
114.23, 55.31, 52.49. HRMS (EI): calcd for C19H14O2N2 F3Cl: 394.0696, found: 394.0684.
5-chloro-3-(4-phenoxyphenyl)-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{3}). It was obtained as a yellow oil in 80 %
yield. 1H NMR (300 MHz, CDCl3): � 8.43-8.40 (s, 1H), 7.39-7.25 (m, 4H), 7.17-7.01 (m, 6H),), 6.92-6.89 (d, 2H, J = 9.12
Hz), 5.06 (s, 2H), 3.81 (s, 3H). 13C NMR (75 MHz, CDCl3): 160.19, 159.86, 156.45, 154.59, 151.60, 131.41, 130.49,
129.88, 129.21, 126.66, 126.50, 124.61, 124.07, 119.74, 117.88, 114.78, 55.50, 52.51. HRMS (EI): calcd for C24H19O3N2Cl:
418.1084, found: 418.1081.
5-chloro-3-(4-methoxyphenyl)-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{4}). It was obtained as a yellow solid m.p. 96-
97 °C in 90 % yield. 1H NMR (300 MHz, CDCl3): � 8.44-8.41 (d, 2H, J = 9.1 Hz), 7.30-7.27 (d, 2H, J = 8.2 Hz), 7.1 (s, 1H),
6.95-6.88 (m, 4H), 5.03 (s, 2H), 3.84 (s, 3H), 3.79 (s, 3H). 13C NMR (75 MHz, CDCl3): 161.78, 160.01, 154.53, 151.60,
131.26, 130.37, 127.75, 126.53, 124.07, 114.62, 113.56, 55.41, 52.36. HRMS (EI): calcd for C19H17O3N2Cl: 356.0928,
found: 356.0938
5-chloro-3-phenyl-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{5}). It was obtained as a yellow oil in 90 % yield. 1H NMR
(300 MHz, CDCl3): � 8.36-8.33 (m, 2H), 7.44-7.42 (m, 3H), 7.31-7.28 (d, 2H, J = 8.2Hz), 7.16 (s, 1H), 6.91-6.88 (d, 2H, J =
9.12 Hz), 5.04 (s, 2H), 3.79 (s, 3H). 13C NMR (75 MHz, CDCl3): 160.10, 154.50, 152.24, 134.94, 130.74, 130.46, 129.37,
128.21, 126.56, 126.35, 125.22, 114.68, 55.41, 52.48. HRMS (EI): calcd for C18H15O2N2Cl: 326.0822, found: 326.0817
5-chloro-3-(2-fluorophenyl)-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{6}). It was obtained as a yellow solid m.p. 69-70
°C in 75 % yield. 1H NMR (400 MHz, CDCl3): � 7.64-7.59 (m, 1H), 7.46-7.39 (m, 1H), 7.33-7.31(d, 2H, J = 8.22 Hz) 7.23-
7.21(m, 2H) 7.18-7.11(m, 1H) 6.92-6.90 (d, 2H, J = 8.22 Hz), 5.05 (s, 2H), 3.80 (s, 3H). 13C NMR (100 MHz, CDCl3):
161.89, 160.17, 159.38, 153.91, 152.25, 131.83, 131.75, 131.25, 131.22, 130.64, 130.52, 126.24, 126.17, 126.11, 123.99,
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123.96, 123.64, 123.55, 116.15, 115.93, 114.70, 55.33, 52.52. HRMS (EI): calcd for C18H14O2N2ClF: 344.0728, found:
344.0734.
5-chloro-3-(3-fluorophenyl)-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{7}). It was obtained as a dark yellow solid 107-
108 °C in 76 % yield. 1H NMR (300 MHz, CDCl3): � 8.23-8.14 (m, 2H), 7.43-7.36 (m, 1H), 7.33-7.30 (d, 2H, J = 8.22 Hz)
7.20-7.14 (m, 2H) 6.92-6.90 (d, 2H, J = 8.22 Hz), 5.07 (s, 2H), 3.81 (s, 3H). 13C NMR (75 MHz, CDCl3): 164.25, 161.02,
160.22, 154.38, 150.57, 130.55, 129.64, 126.53, 126.17, 125.89, 125.13, 117.82, 117.55, 116.45, 116.15, 114.81, 114.38,
55.50, 52.63. HRMS (EI): calcd for C18H14O2N2ClF: 344.0728, found: 344.0732.
5-chloro-3-(2,4-difluorophenyl)-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{8}). It was obtained as a yellow solid m.p.
105-106 °C in 80 % yield. 1H NMR (300 MHz, CDCl3): � 7.66-7.62 (m, 1H), 7.32-7.25 (m, 3H), 6.92-6.89 (m, 4H), 5.04 (s,
2H), 3.80 (s, 3H). 13C NMR (75 MHz, CDCl3): 160.22, 154.28, 153.80, 153.61, 151.66, 151.51, 150.42, 150.23, 148.29,
148.22, 131.83, 130.49, 126.47, 126.05, 125.89, 118.80, 118.52, 114.78, 114.35, 55.44, 52.66. HRMS (EI): calcd for
C18H13O2N2ClF2: 362.0634, found: 362.0630.
5-chloro-3-(3,4-difluorophenyl)-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{9}). It was obtained as a yellow solid m.p. 80-
81 °C in 75 % yield. 1H NMR (300 MHz, CDCl3): � 8.40-8.33 (m, 1H), 8.26 (bs, 1H), 7.31-7.28 d, 2H, J = 8.22 Hz), 7.21-
7.17 (m, 2H) 6.92-6.89 (d, 2H, J = 8.22 Hz), 5.06 (s, 2H), 3.80 (s, 3H). 13C NMR (75 MHz, CDCl3): 160.22, 154.28, 153.80,
153.61, 151.66, 151.51, 150.42, 150.23, 148.29, 148.22, 131.83, 130.49, 126.47, 126.05, 125.89, 118.80, 118.52, 114.78,
114.35, 55.44, 52.66. HRMS (EI): calcd for C18H13O2N2ClF2: 362.0634, found: 362.0629.
5-chloro-3-(2-chlorophenyl)-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{10}). It was obtained as a yellow solid m.p. 98-99
°C in 31 % yield. 1H NMR (300 MHz, CDCl3): � 7.46-7.33 (m, 3H), 7.30-7.27 (m, 4H), 6.91-6.89 (m, 2H), 5.06 (s, 2H), 3.80
(s, 3H). 13C NMR (75 MHz, CDCl3): 160.13, 154.74, 134.54, 133.69, 133.30, 130.95, 130.83, 130.58, 129.85, 126.81,
126.14, 114.71, 55.41, 52.57. HRMS (EI): calcd for C18H14O2N2Cl2: 360.0432, found: 360.0429.
5-chloro-3-(3-chlorophenyl)-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{11}). It was obtained as a yellow solid m.p. 124-
125 °C in 81 % yield. 1H NMR (300 MHz, CDCl3): � 8.39-8.36 (d, 2H, J = 8.22 Hz), 7.40-7.37 (d, 2H, J = 8.22 Hz), 7.30-
7.27 (d, 2H, J = 8.22 Hz), 7.17 (s, 1H), 6.91-6.88 (d, 2H, J = 8.22 Hz), 5.04 (s, 2H), 3.79 (s, 3H) 13C NMR (75 MHz,
CDCl3): 160.16, 154.38, 150.72, 136.95, 133.39, 130.77, 130.46, 128.42, 126.53, 126.20, 125.59, 114.74, 55.44, 52.57.
HRMS (EI): calcd for C18H14O2N2Cl2: 360.0432, found: 360.0431.
5-chloro-3-(4-chlorophenyl)-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{12}). It was obtained as a yellow solid m.p. 128-
129 °C in 73 % yield. 1H NMR (300 MHz, CDCl3): � 8.41 (s, 1H), 8.32-8.29 (d, 1H, J = 8.22 Hz), 7.39-7.35 (m, 2H), 7.31-
7.28 (d, 2H, J = 8.22 Hz), 7.20 (s, 1H), 6.91-6.88 (d, 2H, J = 8.22 Hz), 5.05 (s, 2H), 3.79 (s, 3H) 13C NMR (75 MHz,
CDCl3): 160.16, 154.28, 150.35, 136.52, 134.24, 130.65, 130.46, 129.43, 129.21, 127.48, 126.47, 126.11, 125.99, 114.74,
55.44, 52.60. HRMS (EI): calcd for C18H14O2N2Cl2: 360.0432, found: 360.0428.
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5-chloro-3-(3,4-dichlorophenyl)-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{14}). It was obtained as a yellow solid m.p.
114-115 °C in 89 % yield. 1H NMR (300 MHz, CDCl3): � 8.62-8.61 (m, 1H), 8.35-8.31 (m, 1H), 7.51-7.48 (d, 1H, J = 8.22
Hz), 7.32-7.29 (d, 2H, J = 8.22 Hz), 7.22 (s, 1H), 6.93-6.91 (d, 2H, J = 8.22 Hz), 5.07 (s, 2H), 3.81 (s, 3H) 13C NMR (75
MHz, CDCl3): 160.16, 154.28, 150.35, 136.52, 134.24, 130.65, 130.46, 129.43, 129.21, 127.48, 126.47, 126.11, 125.99,
114.74, 55.44, 52.60. HRMS (EI): calcd for C19H15ON2Cl3: 394.0043, found: 394.0028.
5-chloro-3-(3-bromophenyl)-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{16}). It was obtained as a dark yellow solid m.p.
109-110 °C in 84 % yield. 1H NMR (300 MHz, CDCl3): � 8.55 (s, 1H), 8.37-8.34 (d, 1H, J = 8.22 Hz), 7.57-7.55 (d, 1H, J =
6.39 Hz), 7.31-7.28 (d, 2H, J = 8.22 Hz), 7.32-7.25 (m, 3H), 7.20 (s, 1H), 6.92-6.89 (d, 2H, J = 8.22 Hz), 5.05 (s, 2H), 3.80
(s, 3H). 13C NMR (75 MHz, CDCl3): 160.19, 154.31, 150.32, 136.77, 133.60, 132.11, 130.49, 129.73, 127.97, 126.56,
126.11, 126.02, 122.39,114.78, 55.47, 52.66. HRMS (EI): calcd for C18H14O2N2ClBr: 403.9927, found: 403.9930.
5-chloro-3-(2-methylphenyl)-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{17}). It was obtained as a yellow solid m.p. 115-
116 °C in 28 % yield. 1H NMR (400 MHz, CDCl3): � 7.46-7.44 (d, 1H, J = 7.4 Hz), 7.31-7.29 (m, 3H), 7.25-7.23 (m, 3H),
6.91-6.89 (d, 2H, J = 8.7), 5.03 (s, 2H), 3.80 (s, 3H), 2.31 (s, 3H). 13C NMR (100 MHz, CDCl3): 161.27, 157.08, 155.46,
137.20, 134.95, 130.74, 130.55, 129.70, 126.50, 126.17, 125.61, 114.80, 55.46, 52.57, 20.11. HRMS (EI): calcd for
C19H17O2N2Cl: 340.0978, found: 340.0979.
5-chloro-3-(3-methylphenyl)-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{18}). It was obtained as a yellow solid m.p. 151-
152 °C in 81 % yield. 1H NMR (300 MHz, CDCl3): � 8.17-8.15 (bs, 2H), 7.34-7.24 (m, 4H), 7.14 (s, 1H), 6.90-6.87 (m, 2H),
5.02 (s, 2H), 3.78 (s, 3H), 2.39 (s, 3H). 13C NMR (75 MHz, CDCl3): 160.04, 154.47, 152.46, 137.77, 134.88, 131.56,
129.76, 128.06, 126.59, 126.41, 125.10, 114.62, 55.38, 52.39, 21.56. HRMS (EI): calcd for C19H17O2N2Cl: 340.0978, found:
340.0980.
5-chloro-3-(4-methylphenyl)-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{19}). It was obtained as a yellow solid m.p. 108-
109 °C in 85 % yield. 1H NMR (300 MHz, CDCl3): � 8.31-8.28 (d, 2H, J = 8.22 Hz), 7.31-7.28 (d, 2H, J = 9.12 Hz), 7.22-
7.12 (d, 2H, J = 8.22 Hz), 7.13 (s, 1H), 6.91-6.88 (d, 2H, J = 9.15 Hz), 5.04 (s, 2H), 3.80 (s, 3H), 2.39 (s, 3H). 13C NMR (75
MHz, CDCl3): 160.13, 154.59, 152.30, 141.22, 132.32, 130.46, 129.40, 129.0, 126.56, 124.71, 114.71, 55.47, 52.45, 21.65.
HRMS (EI): calcd for C19H17O2N2Cl: 340.0978, found: 340.0979.
5-chloro-3-(3,4-dimethylphenyl)-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{20}). It was obtained as a yellow solid m.p.
179-180 °C in 80 % yield. 1H NMR (300 MHz, CDCl3): � 7.96 (s, 2H), 7.32-7.29 (d, 2H, J = 9.15 Hz), 7.14 (s, 1H), 7.09 (s,
1H), 6.91-6.88 (d, 2H, J = 9.12 Hz), 5.05 (s, 2H), 3.80 (s, 3H), 2.36 (s, 6H). 13C NMR (75 MHz, CDCl3): 160.10, 154.56,
152.82, 137.68, 134.88, 132.60, 130.43, 127.11, 126.50, 124.89, 114.71, 55.44, 52.42, 21.50. HRMS (EI): calcd for
C20H19O2N2Cl: 354.1135, found: 354.1133.
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5-chloro-3-(4-tert.butylphenyl)-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{21}). It was obtained as a yellow solid m.p.
98-99 °C in 96 % yield. 1H NMR (300 MHz, CDCl3): � 8.31-8.28 (d, 2H, J = 8.22 Hz), 7.46-7.43 (d, 2H, J = 9.13 Hz), 7.30-
7.20 (d, 2H, J = 8.22 Hz), 7.13 (s, 1H), 6.90-6.87 (d, 2H, J = 9.15 Hz), 5.04 (s, 2H), 3.79 (s, 3H), 1.33 (s, 9H). 13C NMR (75
MHz, CDCl3): 160.10, 154.56, 154.16, 152.40, 132.26, 130.43, 129.18, 126.56, 125.22, 124.74, 114.68, 55.44, 52.39, 34.97,
31.25. HRMS (EI): calcd for C22H23O2N2Cl: 382.1448, found: 382.1447.
5-chloro-3-(5-methylthiophene)-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{23}). It was obtained as a yellow solid m.p.
104-105 °C in 64 % yield. 1H NMR (300 MHz, CDCl3): � 8.19-8.17 (d, 1H, J = 3.66 Hz), 7.31-7.28 (d, 2H, J = 8.22 Hz) 7.03
(s, 1H), 6.92-6.89 (d, 2H, J = 8.22 Hz), 6.83-6.81 (d, 1H, J = 3.66), 5.07 (s, 2H), 3.81 (s, 3H), 2.54 (s, 3H). 13C NMR (75
MHz, CDCl3): 160.07, 153.16, 147.89, 147.58, 135.98, 132.44, 130.46, 130.40, 126.81, 126.50, 122.69, 114.78, 55.44,
52.24, 15.74. HRMS (EI): calcd for C17H15O2N2ClS: 346.0542, found: 346.0540.
5-chloro-3-(1- naphthalene)-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{26}). It was obtained as a yellow solid m.p. 173-
174 °C in 90 % yield. 1H NMR (300 MHz, CDCl3): � 7.93-7.84 (m, 3H), 7.79-7.76 (d, 1H, J = 7.29 Hz), 7.54-7.45 (m, 4H),
7.32-7.25 (m, 2H), 6.90-6.87 (d, 2H, J = 9.15), 5.01 (s, 2H), 3.78 (s, 3H). 13C NMR (75 MHz, CDCl3): 160.19, 155.78,
154.89, 133.84, 132.44, 131.07, 130.65, 128.64, 128.39, 126.75, 126.32, 126.08, 125.95, 125.22, 124.98, 114.71, 55.44,
52.69. HRMS (EI): calcd for C22H17O2N2Cl: 376.0979, found: 376.0977.
5-chloro-3-(2-naphthalene)-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{27}). It was obtained as a yellow solid m.p. 156-
157 °C in 88 % yield. 1H NMR (300 MHz, CDCl3): � 8.38-8.35 (m, 1H)7.97-7.95 (m, 1H), 7.87-7.81 (m, 3H), 7.52-7.48 (m,
2H), 7.33-7.30 (d, 2H, J = 8.22 Hz), 7.17 (s, 1H) 6.92-6.89 (d, 2H, J = 9.15 Hz), 5.08 (s, 2H), 3.79 (s, 3H). 13C NMR (75
MHz, CDCl3): 160.16, 154.74, 151.66, 134.48, 133.02, 132.35, 130.68, 130.46, 129.67, 129.46, 127.81, 127.66, 126.75,
126.41, 126.32, 125.71, 125.10, 114.78, 55.47, 52.57. HRMS (EI): calcd for C22H17O2N2Cl: 376.0979, found: 376.0979.
5-chloro-3-(2-ethoxycarbonyl)-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{28}). It was obtained as a yellow oil in 26 %
yield. 1H NMR (300 MHz, CDCl3): � 7.97-7.95 (d, 1H, J = 8.22 Hz), 7.617.52 (m, 3H), 7.32-7.29 (d, 2H J = 9.15 Hz), 6.90-
6.87 (d, 2H, J = 9.12 Hz), 4.98 (s, 2H), 4.23-4.16 (q, 2H, J = 6.8 Hz), 3.79 (s, 3H), 1.43-1.38 (t, 3H, J = 7.29 Hz). 13C NMR
(75 MHz, CDCl3): 166.32, 160.13, 154.38, 150.72, 138.84, 131.86, 130.46, 129.24, 126.56, 126.29, 126.11, 114.71,61.22,
55.41, 52.60, 14.40. HRMS (EI): calcd for C21H19O4N2Cl: 398.1033, found: 398.1028.
5-chloro-3-(4- ethoxycarbonyl)-1-(4-methoxybenzyl)-2(1H)-pyrazinone (3{29}). It was obtained as a yellow solid m.p.
117-118 °C in 90 % yield. 1H NMR (300 MHz, CDCl3): � 8.48-8.45 (d, 2H, J = 8.22 Hz), 8.09-8.07 (d, 2H, J = 8.22 Hz),
7.32-7.29 (d, 3H, J = 9.15 Hz), 6.91-6.88 (d, 2H, J = 9.15 Hz), 5.06 (s, 2H), 4.42-4.35 (q, 2H, J = 6.8 Hz), 3.79 (s, 3H),
1.22-1.18 (t, 3H, J = 7.29 Hz). 13C NMR (75 MHz, CDCl3): 167.05, 160.04, 157.60, 154.80, 135.98, 133.57, 131.47, 130.49,
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130.31, 129.73, 129.52, 126.47, 125.47, 114.59, 61.25, 55.41, 52.30, 14.13. HRMS (EI): calcd for C21H19O4N2Cl: 398.1033,
found: 398.1028.
5-chloro-1-(cyclohexyl)-3-(3-ethoxyphenyl)-2(1H)-pyrazinone (3{30}). It was obtained as a yellow oil in 90 % yield. 1H
NMR (300 MHz, CDCl3): � 7.97 (s, 2H), 7.35-7.30 (t, 1H, J=8.22 Hz), 7.27(s, 1H), 7.00-6.97 (m, 1H), 4.84-4.81 (m, 1H),
4.13-4.06 (q, 2H, J = 7.32 Hz), 2.00-1.92 (m, 4H), 1.80-1.76 (m,1H), 1.54-1.39 (m, 7H), 1.27-1.20.(m, 1H) 13C NMR (75
MHz, CDCl3): 158.76, 154.04, 151.45, 136.43, 129.12, 126.75, 122.39, 121.93, 117.73, 114.78, 63.69, 55.38, 32.25, 25.74,
25.34, 14.95. HRMS (EI): calcd for C18H21O2N2Cl: 332.1292, found: 332.1300.
5-chloro-1-(cyclohexylmethyl)-3-(3-ethoxyphenyl)-2(1H)-pyrazinone (3{31}). It was obtained as a yellow solid m.p. 79-
80 °C in 89 % yield. 1H NMR (300 MHz, CDCl3): � 7.99-7.97 (m, 2H), 7.35-7.30 (t, 1H, J = 8.22 Hz), 7.27(s, 1H), 7.01-6.97
(m, 1H), 4.13-4.061 (q, 2H, J = 6.42 Hz), 3.78-3.76 (d, 2H, J = 7.32 Hz), 1.91-1.85 (m, 1H), 1.72-1.69 (m,6H), 1.44-1.39 (t,
4H, J = 7.29 Hz), 1.25-1.21.(m, 2H), 1.06-0.99.(m, 2H). 13C NMR (75 MHz, CDCl3): 158.76, 154.56, 151.76, 136.22,
129.12, 126.62, 125.95, 121.90, 117.70, 114.81, 63.66, 56.93, 36.76, 30.64, 26.19, 25.61, 14.92. HRMS (EI): calcd for
C19H23O2N2Cl: 346.1448, found: 346.1450.
5-chloro-3-(3-ethoxyphenyl)-1-(3-phenylpropyl)-2(1H)-pyrazinone (3{32}). It was obtained as a yellow oil in 92 % yield.
1H NMR (300 MHz, CDCl3): � 7.98-7.95 (m, 1H), 7.36-7.18 (m, 7H), 7.12(s, 1H), 7.02-6.98 (m, 1H), 4.14-4.07 (q, 2H, J =
7.32 Hz), 3.99-3.94 (t, 2H, J = 7.29 Hz), 2.76-2.71 (t, 4H, J = 7.29 Hz), 2.21-2.11 (p, 2H, J = 7.29 Hz) 1.45-1.40 (t, 2H, J =
7.29 Hz). 13C NMR (75 MHz, CDCl3): 158.76, 154.38, 151.69, 140.15, 136.13, 129.15, 128.73, 128.36, 126.50, 126.29,
126.05, 121.87, 117.73, 114.78, 63.66, 50.41, 32.88, 29.76, 14.92. HRMS (EI): calcd for C21H21O2N2Cl: 368.1291, found:
368.1288.
1-benzyl-5-chloro-3-(3-ethoxyphenyl)-6-methyl-2(1H)-pyrazinone (3{33}). It was obtained as a yellow solid m.p. 135-136
°C in 91 % yield. 1H NMR (300 MHz, CDCl3): � 8.01-7.99 (m, 2H), 7.36-7.31 (m, 4H), 7.26-7.25(m, 2H), 6.99-6.97 (d, 1H,
J = 7.29 Hz), 5.40 (s, 2H), 4.13-4.06 (q, 2H, J = 7.32 Hz), 2.44 (s, 3H), 1.44-1.39 (t, 2H, J = 7.29 Hz). 13C NMR (75 MHz,
CDCl3): 158.82, 155.47, 148.34, 136.43, 135.09, 134.76, 129.18, 128.09, 126.81, 126.62, 121.66, 119.65, 117.24, 114.62,
63.66, 49.10, 17.21, 14.95. HRMS (EI): calcd for C20H19O2N2Cl: 354.1135, found: 354.1132.
5-chloro-3-(3-ethoxyphenyl)-1,6-dimethyl-2(1H)-pyrazinone (3{34}). It was obtained as a yellow solid m.p. 155-156 °C in
94 % yield. 1H NMR (300 MHz, CDCl3): � 7.94 (s, 1H), 7.35-7.30 (t, 1H, J = 8.22 Hz), 7.26(s, 1H), 6.98-6.96 (d, 1H, J =
7.29 Hz), 4.14-4.07 (q, 2H, J = 7.32 Hz), 3.64 (s, 3H), 2.5 (s, 3H), 1.45-1.40 (t, 2H, J = 7.29 Hz). 13C NMR (75 MHz,
CDCl3): 158.73, 155.32, 147.28, 136.43, 135.15, 129.06, 126.11, 121.48, 117.03, 114.41, 63.57, 32.86, 17.39, 14.92. HRMS
(EI): calcd for C14H15O2N2Cl: 278.0822, found: 278.0824.
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S8
1H and 13C
spectra for compound 3{1}
N NO
Cl
OM
e
OE
t
1.8151
3.1526
0.9245
0.9200
1.9592
1.8286
1.9498
2.8788
3.0000
Integral
7.99597.97597.9555
7.34087.32097.29547.27417.25057.14387.00086.99676.98046.89826.8773
5.0351
4.11394.09674.07944.06223.7848
1.42911.41191.3946
0.0005
(ppm)
0.40.8
1.21.6
2.02.4
2.83.2
3.64.0
4.44.8
5.25.6
6.06.4
6.87.2
7.68.0
8.4
N NO
Cl
OM
e
OE
t
160.1377158.7974
154.5023
151.9130
136.1948
130.4680129.1886126.4775126.4166125.3200
121.9387
117.7045
114.8107114.7193
77.586577.160076.7335
63.6655
55.4408
52.4556
14.9267
(ppm)
510
1520
2530
3540
4550
5560
6570
7580
8590
95100
105110
115120
125130
135140
145150
155160
165
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S9
1H and 13C
spectra for compound 3{2}
160.3514
154.4140
150.3496
135.6693132.5603132.1281130.5205128.7158127.1461126.6229126.2514
114.8847
77.478577.160076.8491
55.4731
52.6522
(ppm)
010
2030
4050
6070
8090
100110
120130
140150
160170
N NO
Cl
OM
e
CF
3
0.7158
0.8618
1.0389
1.3354
2.3970
0.8937
1.8792
2.0258
2.9868
Integral
8.72818.63078.6033
7.71137.68707.58357.55617.5317
7.32777.30037.25777.23346.93206.9046
5.0810
3.8085
-0.0000
(ppm)
0.40.8
1.21.6
2.02.4
2.83.2
3.64.0
4.44.8
5.25.6
6.06.4
6.87.2
7.68.0
8.48.8
9.29.6
10.0
N NO
Cl
OM
e
CF
3
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S10
1H and 13C
spectra for compound 3{3}
N NO
Cl
OM
e
OP
h
1.6849
4.2044
2.7156
4.2161
2.2030
2.0702
3.0000
Integral
8.43288.4024
7.39177.36437.33697.32777.30037.25777.17257.14207.07517.01726.92896.89856.6641
5.0658
3.8115
-0.0000
(ppm)
0.40.8
1.21.6
2.02.4
2.83.2
3.64.0
4.44.8
5.25.6
6.06.4
6.87.2
7.68.0
8.48.8
N NO
Cl
OM
e
OP
h
160.1986159.8635
156.4518154.5937
151.6084
131.4123130.4985130.0111129.8892129.2191
126.6603126.5080124.6193124.0710
119.7455117.8873
114.7802
77.586577.160076.7335
55.5017
52.5165
(ppm)
510
1520
2530
3540
4550
5560
6570
7580
8590
95100
105110
115120
125130
135140
145150
155160
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S11
1H and 13C
spectra for compound 3{4}
N NO
Cl
OM
e
OM
e
161.7826160.0158
154.5327
151.6084
131.2600130.3766127.7569126.5384
124.0710
114.6279113.5617
77.556077.160076.7335
55.4104
52.3642
(ppm)
010
2030
4050
6070
8090
100110
120130
140150
160
N NO
Cl
OM
e
OM
e
1.8431
2.1274
0.9574
4.1015
1.8844
3.0701
3.0000
Integral
8.44818.4176
7.30647.2790
7.10256.95026.91986.90766.8802
5.0353
3.84813.7933
-0.0000
(ppm)
0.40.8
1.21.6
2.02.4
2.83.2
3.64.0
4.44.8
5.25.6
6.06.4
6.87.2
7.68.0
8.48.8
9.29.6
10.0
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S12
1H and 13C
spectra for compound 3{5}
N NO
Cl
OM
e
2.0171
3.2914
2.3989
0.9157
1.8575
1.6530
3.0000
Integral
8.36598.35068.3385
7.44347.42217.31567.28827.1664
6.91376.8833
5.0445
3.7933
-0.0000
(ppm)
0.40.8
1.21.6
2.02.4
2.83.2
3.64.0
4.44.8
5.25.6
6.06.4
6.87.2
7.68.0
8.48.8
N NO
Cl
OM
e
160.1072
154.5023152.2481
134.9459131.2600130.7421130.4680128.5794128.2138126.5689126.3557125.2286
114.6888114.2928
77.586577.160076.7335
55.4104
52.4860
(ppm)
010
2030
4050
6070
8090
100110
120130
140150
160170
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S13
1H and 13C
spectra for compound 3{6}
N NO
Cl
OM
e
F
162.3614160.2291159.0411
154.0149152.3395
132.0215131.8997131.3514130.6812126.3861126.2947126.1120124.1624124.1015123.6141123.4313
116.3033116.0291114.7802
77.586577.160076.7335
55.4713
52.6688
(ppm)
510
1520
2530
3540
4550
5560
6570
7580
8590
95100
105110
115120
125130
135140
145150
155160
165
N NO
Cl
OM
e
F
0.9371
0.8278
2.0269
3.2037
1.9548
1.7728
2.9990
Integral
7.56227.53787.51657.36127.34307.26387.23347.18477.15427.11467.10557.07207.04166.85286.8254
4.9806
3.7354
0.0000
(ppm)
0.40.8
1.21.6
2.02.4
2.83.2
3.64.0
4.44.8
5.25.6
6.06.4
6.87.2
7.68.0
8.4
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S14
1H and 13C
spectra for compound 3{7}
1.9914
1.0078
2.1990
2.5524
2.3104
1.9994
3.4566
Integral
8.23508.21068.18328.1497
7.43737.40997.39177.36437.33087.30347.26087.20907.15127.14516.93506.9076
5.0780
3.8146
0.0000
(ppm)
0.40.8
1.21.6
2.02.4
2.83.2
3.64.0
4.44.8
5.25.6
6.06.4
6.87.2
7.68.0
8.48.8
9.29.6
N NO
Cl
OM
e
F
N NO
Cl
OM
e
F
164.2500161.0211160.2291
154.3804
150.5727
136.8954130.5594129.6455126.5384126.1729125.8987125.1372
117.8264117.5522116.4556116.1510114.8107114.3842
77.586577.160076.7335
55.501752.6383
(ppm)
010
2030
4050
6070
8090
100110
120130
140150
160170
180190
200210
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S15
1H and 13C
spectra for compound 3{8}
1.2012
2.1024
1.0663
3.6544
1.9190
3.0000
Integral
7.68367.66417.64647.6264
7.31687.29637.2396
6.96226.94136.91456.8937
5.2757
5.0432
3.7975
0.0000
(ppm)
0.40.8
1.21.6
2.02.4
2.83.2
3.64.0
4.44.8
5.25.6
6.06.4
6.87.2
7.68.0
N NO
Cl
OM
e
F
F
165.5381163.0282162.4367160.2908160.0178
153.9591
151.2065
135.1385132.6209132.5224132.1053130.4295129.2542126.4409126.2893126.1149
120.9130119.8514
114.7937
111.5710111.5406111.3586111.3207104.8450104.5947104.3369
77.478577.160076.8415
55.4200
52.6902
(ppm)
010
2030
4050
6070
8090
100110
120130
140150
160
N NO
Cl
F
OM
e
F
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S16
1H and 13C
spectra for compound 3{9}
OM
e
NN
O
Cl
FF
1.0877
1.0000
3.0418
0.6804
2.0842
1.8494
2.8532
Integral8.38008.37458.35968.35468.28288.27838.27248.2674
7.30457.28327.25417.21927.19837.17387.15206.91686.8955
5.0546
3.7989
-0.0005
(ppm)
0.00.4
0.81.2
1.62.0
2.42.8
3.23.6
4.04.4
4.85.2
5.66.0
6.46.8
7.27.6
8.08.4
8.8
N NO
Cl
OM
e
Cl
Cl
160.2291159.9549154.2890153.8016153.6189151.6693151.5170150.4204150.2376149.2933148.4099148.2272
131.9301131.8388131.7778130.4984
126.4775126.0510125.8987
118.8011118.5270117.0953116.8516114.7802
77.586577.160076.7335
55.4408
52.6688
(ppm)
010
2030
4050
6070
8090
100110
120130
140150
160
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S17
1H and 13C
spectra for compound 3{10}
N NO
Cl
OM
e
Cl
160.1377
154.7460
134.5498133.6969133.3009132.4480132.3261130.9554130.8335130.5898129.8587128.7621127.5437126.8126126.1424
114.7193
77.586577.160076.7335
55.4103
52.5774
010
2030
4050
6070
8090
100110
120130
140150
160
2.8404
4.3689
2.1372
1.8118
3.0000
7.46177.33697.30957.2760
6.91986.8954
5.0688
3.7993
-0.0000
(ppm)
0.40.8
1.21.6
2.02.4
2.83.2
3.64.0
4.44.8
5.25.6
6.06.4
6.87.2
7.6
N NO
Cl
OM
e
Cl
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S18
1H and 13C
spectra for compound 3{11}
2.1558
2.6340
1.4209
1.0821
2.1632
2.0000
3.2469
Integral
8.39638.3689
7.40087.37347.30647.27907.1786
6.91376.8863
5.0414
3.7963
-0.0000
(ppm)
0.00.4
0.81.2
1.62.0
2.42.8
3.23.6
4.04.4
4.85.2
5.66.0
6.46.8
7.27.6
8.08.4
OM
e
NN
O
Cl
Cl
OM
e
NN
O
Cl
Cl
160.1681
154.3804
150.7250
136.9563133.3923130.7726130.4680128.4270126.5384126.2033125.5941
114.7497
77.586577.160076.7335
55.4408
52.5774
(ppm)
510
1520
2530
3540
4550
5560
6570
7580
8590
95100
105110
115120
125130
135140
145150
155160
165
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S19
1H and 13C
spectra for compound 3{12}
160.1681
154.2890
150.3595
136.5299134.2452130.6508130.4680129.4323129.2191127.4827126.4775126.1120125.9901
114.7497
77.556077.160076.7335
55.4408
52.6079
(ppm)
010
2030
4050
6070
8090
100110
120130
140150
160
N NO
Cl
OM
e
Cl
N NO
Cl
OM
e
Cl
0.8245
0.8858
1.0421
3.1179
0.9658
1.8875
1.7513
3.0000
Integral
8.55778.37208.3446
7.57747.55307.32477.31567.29737.28827.25777.20296.92296.8955
5.0567
3.8054
0.0000
(ppm)
0.00.4
0.81.2
1.62.0
2.42.8
3.23.6
4.04.4
4.85.2
5.66.0
6.46.8
7.27.6
8.08.4
8.89.2
9.610.0
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S20
1H and 13C
spectra for compound 3{14}
N NO
Cl
OM
e
Cl
Cl
160.2900
154.2890
149.2933
135.0068134.7326132.6003131.1381130.5289130.1938128.5794126.5689126.2033126.0206
114.8411
77.586577.160076.7335
55.5017
52.7297
(ppm)
1020
3040
5060
7080
90100
110120
130140
150160
N NO
Cl
OM
e
Cl
Cl
0.8439
0.9018
1.0765
1.9709
1.0102
1.9127
1.8546
3.0000
Integral
8.62168.61558.35068.34468.3232
7.51047.4830
7.32477.29737.26087.22426.93816.9107
5.0749
3.8176
-0.0000
(ppm)
0.40.8
1.21.6
2.02.4
2.83.2
3.64.0
4.44.8
5.25.6
6.06.4
6.87.2
7.68.0
8.48.8
9.29.6
10.010.4
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S21
1H and 13C
spectra for compound 3{16}
N NO
Cl
OM
e
Br
160.1986
154.3195
150.3290
136.7736133.6055132.1129130.4984129.7369127.9701126.5689126.1120126.0206
122.3956
114.7802
77.586577.160076.7335
55.4713
52.6383
(ppm)
010
2030
4050
6070
8090
100110
120130
140150
160 N NO
Cl
OM
e
Br
0.8059
0.8892
1.0163
3.1836
0.9414
1.8956
1.7690
3.0000
Integral
8.55778.37208.3446
7.57747.55307.32477.31567.29737.28827.25777.20296.92296.8955
5.0567
3.8054
0.0000
(ppm)
0.40.8
1.21.6
2.02.4
2.83.2
3.64.0
4.44.8
5.25.6
6.06.4
6.87.2
7.68.0
8.48.8
9.29.6
10.0
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S22
1H and 13C
spectra for compound 3{17}
N NO
Cl
Me
OM
e
160.2756
157.0832
154.4671
137.2010134.9565130.7404130.5584129.7016126.5016126.1755125.6144
114.8088
77.478577.160076.8415
55.4655
52.5764
20.1143
(ppm)
010
2030
4050
6070
8090
100110
120130
140150
160
N NO
Cl
Me
OM
e
1.1585
3.3601
2.7629
1.0618
1.9287
1.9228
2.9994
3.0114
Integral
7.46577.44717.31777.31277.30637.29637.29097.25097.23327.19246.91736.8955
5.0296
3.8030
2.3185
0.0005
(ppm)
0.40.8
1.21.6
2.02.4
2.83.2
3.64.0
4.44.8
5.25.6
6.06.4
6.87.2
7.68.0
8.48.8
9.2
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S23
1H and 13C
spectra for compound 3{18}
N NO
Cl
OM
e
Me
160.0463
154.4718152.4613
137.7788134.8849131.5646130.3766129.7674128.0615126.5993126.4166125.1067
114.6279
77.556077.160076.7335
55.3799
52.3946
21.5674
(ppm)
010
2030
4050
6070
8090
100110
120130
140150
160170
N NO
Cl
OM
e
Me
1.8987
4.1473
1.0051
1.9672
1.9348
2.9714
3.0000
Integral
8.17108.1528
7.34307.31567.30347.29737.27607.26697.24557.14206.90156.8711
5.0262
3.7841
2.3989
0.0000
(ppm)
0.40.8
1.21.6
2.02.4
2.83.2
3.64.0
4.44.8
5.25.6
6.06.4
6.87.2
7.68.0
8.48.8
9.29.6
10.0
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S24
1H and 13C
spectra for compound 3{19}
1.9059
2.2991
2.5804
0.9582
2.0019
1.9657
3.0000
3.0892
Integral
8.31118.2837
7.31867.28827.25167.22427.1299
6.91686.8863
5.0475
3.8024
2.3929
-0.0000
(ppm)
0.40.8
1.21.6
2.02.4
2.83.2
3.64.0
4.44.8
5.25.6
6.06.4
6.87.2
7.68.0
8.48.8
N NO
Cl
OM
e
Me
N NO
Cl
OM
e
Me
160.1377
154.5937152.3090
141.2210
132.3261130.4680129.4018129.0058
126.5689124.7107
114.7193
77.586577.160076.7640
55.4713
52.4556
21.6588
(ppm)
010
2030
4050
6070
8090
100110
120130
140150
160
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S25
1H and 13C
spectra for compound 3{20}
N NO
Cl
OM
e
Me
Me
160.1072
154.5632152.8269
137.6874
134.8849132.6003130.4375
127.1172126.5080124.8935
114.7193
77.556077.160076.7335
55.4408
52.4251
21.5065
(ppm)
010
2030
4050
6070
8090
100110
120130
140150
160
N NO
Cl
OM
e
Me
Me
1.8127
2.2185
1.9892
1.9459
1.8750
2.9629
6.0000
Integral
7.9610
7.32177.29127.25477.14207.0903
6.91986.8894
5.0506
3.8024
2.3685
-0.0000
(ppm)
0.40.8
1.21.6
2.02.4
2.83.2
3.64.0
4.44.8
5.25.6
6.06.4
6.87.2
7.68.0
8.48.8
9.2
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S26
1H and 13C
spectra for compound 3{21}
1.9004
2.2365
2.1878
0.9194
2.0835
1.9105
3.0000
9.3218
Integral
8.31118.2837
7.46477.43437.30957.2821
7.1299
6.90466.8741
5.0414
3.7902
1.3334
0.0000
(ppm)
0.00.4
0.81.2
1.62.0
2.42.8
3.23.6
4.04.4
4.85.2
5.66.0
6.46.8
7.27.6
8.08.4
8.8
OM
e
NN
O
Cl
MeM
eM
e
OM
e
NN
O
Cl
MeM
eM
e
160.1072
154.5632154.1672152.4004
132.2652130.4375129.1886
126.5689125.2286124.7412
114.6888
77.586577.160076.7335
55.4408
52.3946
34.9705
31.2542
(ppm)
010
2030
4050
6070
8090
100110
120130
140150
160
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S27
1H and 13C
spectra for compound 3{23}
N NO
Cl
OM
e
SM
e
160.0768
153.1619
147.8921147.5875
135.9815
132.4480130.4680130.4071126.8126126.5080
122.6698
114.7802
77.586577.160076.7335
55.4408
52.2423
15.7492
(ppm)
010
2030
4050
6070
8090
100110
120130
140150
160
N NO
Cl
OM
e
S
Me
0.8334
1.9190
0.8690
1.9421
1.0086
1.9202
2.9980
2.9964
Integral
8.18938.1771
7.31257.28517.2608
7.03246.92286.89546.83156.8193
5.0719
3.8115
2.5420
-0.0000
(ppm)
0.00.4
0.81.2
1.62.0
2.42.8
3.23.6
4.04.4
4.85.2
5.66.0
6.46.8
7.27.6
8.08.4
8.89.2
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S28
1H and 13C
spectra for compound 3{26}
OM
e
NN
O
Cl
2.5772
1.0889
3.7427
2.1827
1.9260
2.0000
3.0881
Integral
7.93367.90627.88187.86967.86057.84837.79357.76927.54697.52267.49217.48007.47087.45867.32177.29437.25476.90466.8741
5.0140
3.7841
-0.0000
(ppm)
0.00.4
0.81.2
1.62.0
2.42.8
3.23.6
4.04.4
4.85.2
5.66.0
6.46.8
7.27.6
8.08.4
8.8
OM
e
NN
O
Cl
160.1986
155.7817154.8983
133.8492132.4480131.0772130.6508128.6403128.3966126.7517126.3252126.0815125.9597125.2286124.9849
114.7193
77.586577.160076.7335
55.4408
52.6993
(ppm)
010
2030
4050
6070
8090
100110
120130
140150
160170
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S29
1H and 13C
spectra for compound 3{27}
OM
e
NN
O
Cl
1.1672
1.2474
1.4211
2.8123
2.1191
2.4857
1.1020
2.3972
1.9433
3.3495
Integral
9.2122
8.38118.35678.3506
7.97317.95187.87887.84837.81487.52877.52267.51347.50437.48917.48307.33087.30347.25167.17556.92596.8954
5.0840
3.7963
-0.0000
(ppm)
0.00.4
0.81.2
1.62.0
2.42.8
3.23.6
4.04.4
4.85.2
5.66.0
6.46.8
7.27.6
8.08.4
8.89.2
9.6
OM
e
NN
O
Cl
160.1681
154.7460
151.6693
134.4889133.0268132.3566130.6812130.4680129.6760129.4627127.8178127.6655126.7517126.4166126.3252125.7160125.1067
114.7802
77.586577.160076.7335
55.4713
52.5774
(ppm)
010
2030
4050
6070
8090
100110
120130
140150
160
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S30
1H and 13C
spectra for compound 3{28}
167.0525
160.0463
157.6094
154.8069
135.9816133.5751132.1738131.4732130.4984130.3157129.7369129.5237128.7926127.4827126.4775126.2947125.4723
114.5974
77.586577.160076.7335
61.2590
55.4104
52.3033
14.1347
(ppm)
1020
3040
5060
7080
90100
110120
130140
150160
170
N NO
Cl
OM
e
CO
OE
t
N NO
Cl
OM
e
CO
OE
t
0.9468
0.3602
3.2199
2.3156
1.2749
2.0527
1.8464
1.9304
2.9492
3.0000
Integral
7.97627.95187.84837.61707.59267.56527.55007.52267.49527.31867.29127.1907
6.90766.8802
4.9866
4.23164.20734.18294.1616
3.7963
1.22691.20561.1812
-0.0000
(ppm)
0.00.4
0.81.2
1.62.0
2.42.8
3.23.6
4.04.4
4.85.2
5.66.0
6.46.8
7.27.6
8.08.4
8.8
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S31
1H and 13C
spectra for compound 3{29}
N NO
Cl
CO
OE
t
OM
e
166.3214
160.1377
154.3804
150.7250
138.8450
131.8692130.4680129.2495126.5689126.2947126.1120
114.7193
77.586577.160076.7640
61.2285
55.4104
52.6079
14.4089
(ppm)
010
2030
4050
6070
8090
100110
120130
140150
160170
1.7862
1.8899
1.8358
0.9079
1.7859
1.7822
1.9920
2.7196
3.0000
Integral
8.48168.4542
8.09808.0706
7.32177.29127.2425
6.91686.8863
5.0627
4.42654.40524.38084.3565
3.7933
1.43081.40651.3852
0.0000
(ppm)
0.40.8
1.21.6
2.02.4
2.83.2
3.64.0
4.44.8
5.25.6
6.06.4
6.87.2
7.68.0
8.48.8
9.29.6
10.0
N NO
Cl
OM
e
CO
OE
t
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S32
1H and 13C
spectra for compound 3{30}
N NO
Cl
OE
t
158.7669
154.0453
151.4561
136.4385
129.5237129.1277
126.7517
122.3956121.9387
117.7350
114.7802
77.586577.160076.7640
63.6959
55.8368
32.2595
25.740625.3446
14.9572
(ppm)
010
2030
4050
6070
8090
100110
120130
140150
N NO
Cl
OE
t
1.8819
1.2204
0.8713
0.9142
0.8898
1.9740
3.9147
1.3662
3.4092
3.6085
1.7745
Integral
7.9730
7.35507.32767.30027.26677.00807.00196.9745
4.84654.8191
4.13714.11284.09154.0671
2.00611.96961.92091.80521.76251.54341.50681.48251.44291.42161.39721.27551.24501.2054
-0.0001
(ppm)
0.40.8
1.21.6
2.02.4
2.83.2
3.64.0
4.44.8
5.25.6
6.06.4
6.87.2
7.68.0
8.48.8
9.29.6
10.0
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S33
1H and 13C
spectra for compound 3{31}
158.7669
154.5632
151.7607
136.2252
129.1277126.6298125.9596
121.9082
117.7045
114.8107
77.586577.160076.7335
63.6655
56.9334
36.7678
30.6450
26.197625.6188
14.9267
(ppm)
010
2030
4050
6070
8090
100110
120130
140150
160
N NO
Cl
OE
t
N NO
Cl
OE
t
1.6592
1.2483
0.8842
0.8705
1.9840
1.8157
1.5299
6.0208
3.1590
2.4282
1.9558
Integral
7.99457.9701
7.35517.32777.30037.26387.14817.01117.00206.9776
4.13424.11294.08864.0672
3.78723.7628
1.91791.90581.89361.88141.86621.85711.72921.69571.44301.42171.39741.25731.21771.06551.02900.9955
0.0000
(ppm)
0.40.8
1.21.6
2.02.4
2.83.2
3.64.0
4.44.8
5.25.6
6.06.4
6.87.2
7.68.0
8.48.8
9.29.6
10.0
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S34
1H and 13C
spectra for compound 3{32}
N NO
Cl
OE
t
158.7669
154.3804
151.6998
140.1548
136.1339129.1581128.7317128.3661126.5080126.2947126.0510
121.8778
117.7350
114.7802
77.586577.160076.7335
63.6655
50.4146
32.8382
29.7616
14.9267
(ppm)
010
2030
4050
6070
8090
100110
120130
140150
160
N NO
Cl
OE
t
1.5637
3.0022
3.2108
0.9553
0.8754
2.0021
1.8320
1.9061
1.8832
3.1147
Integral
8.00137.97397.38037.35297.32557.29817.27687.25557.22817.20077.14287.03637.03027.0058
4.15944.13504.11374.08934.01323.98893.9615
2.78032.75592.7285
2.23532.20792.18362.15922.1349
1.46821.44691.4225
0.0160
(ppm)
0.40.8
1.21.6
2.02.4
2.83.2
3.64.0
4.44.8
5.25.6
6.06.4
6.87.2
7.68.0
8.48.8
9.29.6
10.0
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S35
1H and 13C
spectra for compound 3{33}
N NO
Cl
OE
t
Me
158.8278
155.4770
148.3490
136.4385135.0982134.7631
129.1886128.0920126.8126126.6298
121.6645119.6541
117.2476
114.6279113.4703
77.586577.160076.7335
63.6655
49.1048
17.211414.9572
(ppm)
010
2030
4050
6070
8090
100110
120130
140150
160
1.8990
4.2961
1.9187
0.9258
1.8922
1.9825
2.8642
3.0000
Integral
8.01587.9945
7.36127.33997.31567.26087.25477.20607.18476.99906.9716
5.4007
4.13734.11294.09164.0672
2.4446
1.44301.42171.3974
-0.0000
(ppm)
0.40.8
1.21.6
2.02.4
2.83.2
3.64.0
4.44.8
5.25.6
6.06.4
6.87.2
7.68.0
8.48.8
9.29.6
10.010.4
N NO
Cl
OE
t
Me
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S36
1H and 13C
spectra for compound 3{34}
158.7364
155.3247
147.2828
136.4385135.1591
129.0667
126.1120
121.4818
117.0344
114.4147
77.586577.160076.7640
63.5741
32.8687
17.394114.9267
(ppm)
010
2030
4050
6070
8090
100110
120130
140150
160170
180
N NO
Cl
Me
OE
t
Me
N NO
Cl
OE
t
Me
Me
1.3677
1.0141
0.9738
0.8603
1.9235
2.6723
2.7027
2.9757
Integral
7.9427
7.35517.32777.30347.2638
6.98686.9624
4.14034.11904.09774.0733
3.6441
2.5420
1.44911.42781.4034
-0.0000
(ppm)
0.40.8
1.21.6
2.02.4
2.83.2
3.64.0
4.44.8
5.25.6
6.06.4
6.87.2
7.68.0
8.48.8
9.29.6
10.010.4
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY
S37
PRIVILEGED DOCUMENT FOR REVIEW PURPOSES ONLY