反应详情

温度

5 °C

Oxalyl chloride (20.2 mL, 231 mmol) was added to a suspension of 4-morpholin-4-ylbenzoic acid (7.98 g, 38.5 mmol) in dry dichloromethane (DCM, 210 mL) and dimethylformamide (DMF, 0.04 mL). After refluxing the mixture for 6.5 hours, volatiles were carefully removed under reduced pressure (taking up the residue three times with toluene). The resulting 4-morpholin-4-ylbenzoyl chloride hydrochloride was added portion-wise (in about 0.5 hours) to a suspension of 5-tert-butyl 1-ethyl 3-amino-1H-thieno[2,3-c]pyrazole-1,5-dicarboxylate (6.0 g, 19.3 mmol) in dry DCM (200 mL) and pyridine (23.2 mL, 289 mmol), under stirring at 5° C. The resulting suspension was stirred for 20 hours at room temperature. 300 mL of DCM and 300 mL of aqueous sodium bicarbonate were then added to the reaction mixture; the organic layer was separated, washed with brine, dried over sodium sulphate and evaporated. Purification by chromatography (DCM/ethyl acetate 7:3) gave 4.05 g of the title compound.

1. temperatureAfter refluxing the mixture for 6.5 hours
2. customvolatiles were carefully removed under reduced pressure (
3. additionThe resulting 4-morpholin-4-ylbenzoyl chloride hydrochloride was added portion-wise (in about 0.5 hours)
4. stirringThe resulting suspension was stirred for 20 hours at room temperature
5. customthe organic layer was separated
6. washwashed with brine
7. dry with materialdried over sodium sulphate
8. customevaporated
9. customPurification by chromatography (DCM/ethyl acetate 7:3)