Ethylmorpholine → [(2,3-Dichloro-4-fluorophenyl)methyl]-1-methyl-5-oxoprolinamide

1-methyl-5-oxoproline (0.060 g, 0.42 mmol, prepared as described above for example 51) was dissolved in dichloromethane (5 ml) and to this was added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.096 g, 0.5 mmol), 1-hydroxybenzotriazole (0.068 g, 0.5 mmol), and N-ethyl morpholine (0.160 ml, 1.26 mmol). The mixture was stirred for ˜10 minutes and then [(2,3-dichloro-4-fluorophenyl)methyl]amine hydrochloride (0.081 g, 0.42 mmol, prepared as described previously for example 48) was added and the mixture was left to stir overnight (˜17 hrs) and then over the weekend. The mixture was then treated with saturated aqueous sodium hydrogen carbonate (˜3 ml) and stirred vigorously for 10 minutes. The organic layer was separated using a hydrophobic frit, washing the aqueous with additional dichloromethane (˜2 ml). The combined organic fractions were concentrated to give a cream coloured solid. The solid was partitioned between ethyl acetate (˜20 ml) and water (˜10 ml) and the organic layer was then separated by passing through a phase separator and concentrated to give pure -[(2,3-dichloro-4-fluorophenyl)methyl]-1-methyl-5-oxoprolinamide as an off-white solid.

1. additionwas added
2. waitthe mixture was left
3. stirringto stir overnight (˜17 hrs)
4. stirringstirred vigorously for 10 minutes
5. customThe organic layer was separated
6. washwashing the aqueous with additional dichloromethane (˜2 ml)
7. concentrationThe combined organic fractions were concentrated
8. customto give a cream
9. customThe solid was partitioned between ethyl acetate (˜20 ml) and water (˜10 ml)
10. customthe organic layer was then separated
11. concentrationconcentrated

ORDレコード

ord-d6f739cb8cd34c4bb553b2baa63f4c79

出典データセット

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08048907B2