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Supporting Information:

Lead Optimization of 4-Acetylamino-2-(3,5-dimethylpyrazol-1-yl)-6-pyridylpyrimidines as A2A Adenosine Receptor Antagonists for the Treatment of Parkinson’s Disease Xiaohu Zhang, John E. Tellew, Zhiyong Luo, Manisha Moorjani, Emily Lin, Marion C. Lanier, Yongsheng Chen, John P. Williams, John Saunders, Sandra M. Lechner, Stacy Markison, Tanya Joswig, Robert Petroski , Jaime Piercey , William Kargo , Siobhan Malany, Mark Santos, Raymond S. Gross, Jenny Wen, Kayvon Jalali, Zhihong O’Brien, Carol E. Stotz, María I. Crespo, José-Luis Díaz, and Deborah H. Slee.

†Medicinal Chemistry, Neurocrine Biosciences; ⊥Neuroscience, Neurocrine Biosciences; δPharmacology, Neurocrine Biosciences; γPreclinical Development, Neurocrine Biosciences; ΠPharmaceutical Development, Neurocrine Biosciences; θAlmirall Research Center

Table of Contents: Table of compound purities Page S2 NMR and LCMS data for key compounds Page S3

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Compound Purity Compound LCMS

Method #

% purity CHN

6a 2 97 6b 4 100 6c 4 99 6d 2 99 6e 3 100 6f 3 100 6g 3 100 Anal. (C17H18N602.HCl.2H2O) C, H, N. 6h 3 100 7 2 96

9a 4 98 Anal. (C21H25N703.HCl.H2O) C, H, N. 9b 3 96 9c 2 100 9d 4 100 17 2 100 14 2 95 15 2 100 16a 2 100 16b 2 100 16c 2 100 16d 2 100 ESHRMS m/z 378.2040, [M + H]+ requires

378.2037 16e 2 98 ESHRMS m/z 392.2188, [M + H]+ requires

392.2193 16f 1 100 16g 2 100 16h 2 100 Anal. (C22H27N702.1/4HOAc) C, H, N. 16i 2 90 ESHRMS m/z 394.1995, [M + H]+ requires

394.1986 16j 3 100 16k 3 100 Anal. (C21H25N702) C, H, N.

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