[Cl:1][C:2]1[C:7]([C:8]([OH:10])=O)=[C:6]([Cl:11])[N:5]=[CH:4][N:3]=1.S(Cl)(Cl)=O.[CH3:16][NH:17][CH2:18][C:19]#[CH:20].C(N(CC)CC)C>C(Cl)Cl.CN(C=O)C>[Cl:11][C:6]1[C:7]([C:8]([N:17]([CH3:16])[CH2:18][C:19]#[CH:20])=[O:10])=[C:2]([Cl:1])[N:3]=[CH:4][N:5]=1A solution of 4,6-dichloropyrimidine-5-carboxylic acid (Compound 310G, 15.0 g, 77.7 mmol) and thionyl chloride (28.3 mL, 389 mmol) was refluxed in DCM (100 mL) for 2 h. The reaction mixture was concentrated in vacuo, taken up in DMF (200 mL) and charged drop-wise with a solution of N-methyl-2-propyn-1-amine (5.4 g, 78 mmol) and triethylamine (21.7 mL, 155 mmol) in DMF at −60° C. and stirred at rt for 24 h. The reaction mixture was partitioned between EtOAc and water and separated. The aqueous layer was extracted with EtOAc (3×) and the combined organic fractions were washed with brine, dried over sodium sulfate, filtered, and concentrated. The compound was purified on an Isco Combiflash to afford 7.66 g, 40% yield, of the title compound. 1H NMR (DMSO-d6, 400 MHz): δ=9.04 (s, 1H), 4.37 (d, J=2.53 Hz, 2H), 3.08 (s, 1H), 2.95 (s, 3H). MS (ES+): m/z 246.0039 [MH+] (TOF, polar).
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