Thionyl Chloride → HCID 178454103, 화합물

2-(3-Chloropyrazin-2-yl)-2-methylpropanoic acid (intermediate 29, 0.302 g, 1.505 mmol) was dissolved in dichloromethane (20 mL) and treated with thionyl chloride (5.0 ml, 68.5 mmol). The solution was heated at reflux for 30 minutes then evaporated to dryness under reduced pressure. Carbon tetrachloride (20 ml) was added to the crude residue and it was evaporated to dryness once more. It was dried under high vacuum for 20 minutes. The crude acid chloride was dissolved in dichloromethane (6 mL) and added slowly to an ice cooled solution of tert-butyl(trans-3-aminocyclobutyl)carbamate (0.280 g, 1.505 mmol) and diisopropylethylamine (2.5 ml, 14.37 mmol) in dichloromethane (10 mL). The solution was stirred for 15 minutes after which the mixture was evaporated to dryness under reduced pressure and the crude dissolved in dry tetrahydrofuran (10 mL). Sodium t-butoxide (1.45 g, 15.09 mmol) was added and the reaction stirred at room temperature. After 30 minutes the reaction was partitioned between water (300 mL) and ethyl acetate (300 mL). The organic was washed with 20% saturated ammonium chloride (200 mL) then dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification using silica chromatography (hexane to ethyl acetate gradient) gave the desired tert-butyl(trans-3-(7,7-dimethyl-6-oxo-6,7-dihydro-5H-pyrrolo[2,3-b]pyrazin-5-yl)cyclobutyl)carbamate (0.462 g, 1.390 mmol, 92% yield). It was dissolved in dichloromethane (10 mL) and treated with trifluoroacetic acid (5 mL). The solution was stirred for 15 minutes. The dark solution was evaporated to dryness under reduced pressure and further dried under high vac. The crude amine was combined with purified using silica chromatography (1-20% (2N ammonia in methanol) in dichloromethane gradient) to give 5-(trans-3-aminocyclobutyl)-7,7-dimethyl-5H-pyrrolo[2,3-b]pyrazin-6(7H)-one (0.294 g, 1.27 mmol, 91% yield).

1. temperatureThe solution was heated
2. temperatureat reflux for 30 minutes
3. customthen evaporated to dryness under reduced pressure
4. additionCarbon tetrachloride (20 ml) was added to the crude residue and it
5. customwas evaporated to dryness once more
6. customIt was dried under high vacuum for 20 minutes
7. dissolutionThe crude acid chloride was dissolved in dichloromethane (6 mL)
8. customwas evaporated to dryness under reduced pressure
9. dissolutionthe crude dissolved in dry tetrahydrofuran (10 mL)
10. stirringthe reaction stirred at room temperature
11. customAfter 30 minutes the reaction was partitioned between water (300 mL) and ethyl acetate (300 mL)
12. washThe organic was washed with 20% saturated ammonium chloride (200 mL)
13. dry with materialthen dried with magnesium sulfate
14. customevaporated to dryness under reduced pressure
15. customPurification

ORD 기록

ord-858369e2b46d490ab3264348386d6068

출처 데이터셋

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09174992B2