Water → 1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-10a-{4-[2-(morpholin-4-yl)ethoxy]phenyl}-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one

温度

0 °C

To generate the acid chloride, oxalyl chloride (0.1 mL, 1.2 mmol) and DMF (1 drop) were added to 3-methyl-1,2-oxazole-4-carboxylic acid (30 mg, 0.24 mmol) in CH2Cl2 (0.5 mL) at 0° C. The suspension was allowed to stir 15 minutes at 0° C. followed by 1 hour at room temperature. The resulting solution was concentrated to give an oil that was further dried under nitrogen. To a chilled suspension of the acid chloride (generated as above, 0.24 mmol) in pyridine (0.5 mL) was added 10a-{4-[2-(morpholin-4-yl)ethoxy]phenyl}-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (20 mg, 75% pure, 0.039 mmol) in pyridine (0.3 mL). The reaction mixture was stirred at 0° C. and then at room temperature. After 2.5 hours an additional batch of acid chloride (0.24 mmol) was prepared as above, diluted in pyridine (0.3 mL) and added to the reaction mixture. The mixture was stirred overnight at room temperature. Water (2 mL) was then added and the mixture extracted with dichloromethane (3×1.5 mL). The organic layers were dried (MgSO4), filtrated and concentrated in vacuo to give a residue that was purified by preparative LCMS (reverse phase, acetonitrile-water containing 0.1% formic acid) to give 1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-10a-{4-[2-(morpholin-4-yl)ethoxy]phenyl}-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (110) (7 mg, yield 36%).

1. waitfollowed by 1 hour at room temperature
2. concentrationThe resulting solution was concentrated
3. customto give an oil that
4. customwas further dried under nitrogen
5. stirringThe reaction mixture was stirred at 0° C.
6. customat room temperature
7. additionadded to the reaction mixture
8. stirringThe mixture was stirred overnight at room temperature
9. extractionthe mixture extracted with dichloromethane (3×1.5 mL)
10. dry with materialThe organic layers were dried (MgSO4)
11. filtrationfiltrated
12. concentrationconcentrated in vacuo
13. customto give a residue that
14. customwas purified by preparative LCMS (reverse phase, acetonitrile-water containing 0.1% formic acid)

ORDレコード

ord-077c525acd0346e5b7b5eb6a686b9bb0

出典データセット

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09163029B2