Yield:345986-38-1 84%

Reaction Conditions:

Stage #1: 2-cyanomethylbenzothiazolewith sodium hydride in tetrahydrofuran at 20; for 1.5 h;
Stage #2: 2,6-Dichloropyrimidine in tetrahydrofuran at 20;

Steps:

A

To a stirred suspension of NaH (60% in oil, 9.2 g, 0.23 mol) in dry THF (200 ml) was added drop wise under inert atmosphere a solution of 1, 3-benzothiazol-2yl-acetonitrile (20 g, 0.15 mol) in dry THF (200 ml). After lh30 stirring at r. t. , a solution of 2, 4-dichloropyri- midine (17.1 g, 0.15 mol) in dry THF (200 ml) was added dropwise. The reaction mixture was allowed to stir under inert atmosphere at r. t. until complete disappearance of the starting material. The reaction was quenched by addition of water and the THF was evaporated. Water was added and the suspension was slightly acidified with aqueous HC1 1M. The precipitate obtained was filtered off and washed thoroughly with water until neutral then with hexane to remove the oil. The crude solid was dried under vacuum at 40°C, affording 28 g (84 %) of the title compound as a light brown powder: mp 246°C dec.; MS: 286.8 (M+1) ; HPLC (Conditions a, 268 nm) 97%, rt. 5. 66 min ;'HNMR (DMSO-d6) 8 13. 25 (br s, 1H, exchangeable), 8.09 (d, J= 4.14 Hz, 1H), 7.90 (d, J = 7.53 Hz, 1H), 7.61 (d, J= 7.92 Hz, 1H), 7.39-7. 34 (m, 1H), 7.20-7. 15 (m, 1H), 6.96 (br d, 1H). CHN analysis: C13H7CIN4S

References:

WO2003/91249,2003,A1 Location in patent:Page/Page column 20-21