反应详情

温度

90 °C

A Barney reactor was charged with Pd(OAc)2 (0.337 mg, 1.50 μmol), Xantphos (0.913 mg, 1.58 μmol) and 4-(4-bromo-2-methylphenyl)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine (33.3 mg, 0.075 mmol, prepared using B from Example #2 step A with ethylhydrazine oxalate, J with 4-bromo-2-methyl-benzaldehyde (AstaTech) and 1-sulfanylpropan-2-one [Enamine] then K with Na(AcO)3BH). The solids were slurried in 1,4-dioxane (0.15 ml) and then sealed in the reactor. The atmosphere was inerted to N2 (5×15 psig) then flushed with NH3 (3×). The reactor was charged with NH3 (80 psig) (˜0.2 g) then with CO (33 psig) for a total pressure of ˜113 psig. The reactor was sealed and heated to about 90° C. with stirring at 750 rpm with a pressure of ˜150 psig. After about 16 h, the reactor was cooled to rt and purged with N2. The crude material was purified by flash chromatography (25 g silica gel; heptane/EtOAc 4:1 to 0:1) to give 4-(1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylbenzamide (0.156 g, 85%) as a mixture of stereoisomers: LC-MS (Table 1, Method g) Rt=2.00 and 2.02 min.; MS m/z: 408.1 and 408.1 (M+H)+.

1. customprepared
2. customsealed in the reactor
3. customthen flushed with NH3 (3×)
4. additionThe reactor was charged with NH3 (80 psig) (˜0.2 g)
5. customThe reactor was sealed
6. temperaturethe reactor was cooled to rt
7. custompurged with N2
8. customThe crude material was purified by flash chromatography (25 g silica gel; heptane/EtOAc 4:1 to 0:1)