反应详情

A suspension of 2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylthieno[3,2-d]pyrimidin-4(3H)-one (250 mg, 0.72 mmol), benzotriazol-1-yloxy-tris(dimethylamino)-phosphonium hexafluorophosphate (415 mg, 0.94 mmol) and 1,8-diazabicycloundec-7-ene (165 mg, 1.08 mmol) in anhydrous N,N-dimethylformamide (10 mL) was stirred at r.t. for 10 min, then a solution of 3-aminomethyl-oxetan-3-ylamine (150 mg, 1.44 mmol) in N,N-dimethylformamide (5 mL) was added dropwise. After the addition was complete, the mixture was heated at 60° C. overnight, then it was diluted with water (50 mL), extracted by dichloromethane, washed by brine, dried with anhydrous sodium sulfate. The solvent was removed and the residue was purified by preparative HPLC to afford N-[(3-aminooxetan-3-yl)methyl]-6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)thieno[3,2-d]pyrimidin-4-amine as a white solid. MS obsd. (ESI+) [(M+H)+] 430, 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.67-7.80 (m, 2H), 7.45 (t, J=5.8 Hz, 2H), 6.82 (s, 1H), 5.21 (d, J=15.4 Hz, 1H), 4.71 (br. s., 1H), 4.63 (d, J=6.3 Hz, 2H), 4.46-4.56 (m, 2H), 4.01 (s, 2H), 3.30-3.49 (m, 4H), 2.55 (s, 3H).

1. additionAfter the addition
2. temperaturethe mixture was heated at 60° C. overnight
3. extractionextracted by dichloromethane
4. washwashed by brine
5. dry with materialdried with anhydrous sodium sulfate
6. customThe solvent was removed
7. customthe residue was purified by preparative HPLC