反应详情

A mixture of (3R,5S)-3,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester (0.92 g), 6-bromomethyl-2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (1 g) and potassium carbonate (1.59 g) in MeCN (10 ml) was heated to reflux for 5 days. The reaction mixture was subsequently cooled, diluted with chloroform, washed with brine and dried (MgSO4), and the solvent was removed in vacuo. The residue was purified by flash column chromatography to yield (3S,5R)-4-(2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-3,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester, 170 (1.2 g). Treatment of this compound with HCl in DCM/MeOH produced 2-chloro-6-(2S,6R)-2,6-dimethyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine, 171, which was then methylated using 37% formaldehyde solution and sodium borohydride in MeOH, furnishing 172.

1. temperaturewas heated
2. temperatureto reflux for 5 days
3. temperatureThe reaction mixture was subsequently cooled
4. washwashed with brine
5. dry with materialdried (MgSO4)
6. customthe solvent was removed in vacuo
7. customThe residue was purified by flash column chromatography