Chlorosuccinimide → 2-Amino-5-chloro-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidine
Reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[N:12]([CH:13]([CH3:15])[CH3:14])[C:11]([CH3:16])=[N:10][CH:9]=2)[CH:5]=[CH:4][N:3]=1.[Cl:17]N1C(=O)CCC1=O>C(O)(=O)C>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[N:12]([CH:13]([CH3:14])[CH3:15])[C:11]([CH3:16])=[N:10][CH:9]=2)[C:5]([Cl:17])=[CH:4][N:3]=1Participants
4
Procedure
A solution of 2-amino-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidine (Method 39 of WO 03/076436; 0.5 g, 2.3 mmol) and N-chlorosuccinimide (0.4 g, 3 mmol) in acetic acid (5 ml) was stirred at 65° C. under nitrogen for 2 hours. Then the reaction mixture was allowed to cool down to room temperature and the solvent was removed under vacuum. The crude was taken up in EtOAc and water then portions of solid potassium carbonate were added to this stirred biphasic solution until pH 8-9 was reached. The two layers were separated, the aqueous layer was extracted once with EtOAc then the organics were combined, washed with brine and dried. Removal of the solvent left a residue, which was purified on silica (MeOH/DCM/EtOAc, from 0/50/50 to 6/47/47). Triturating the foam in ether gave a white solid, which was filtered off. (0.49 g, 85%). NMR (CDCl3): 1.51 (d, 6H), 2.55 (s, 3H), 4.85 (septuplet, 1H), 5.01 (b s, 2H), 7.48 (s, 1H), 8.31 (s, 1H); m/z 252 (35Cl), 254 (37Cl); m/z 250 (35Cl), 252 (37Cl).