Diisopropylethylamine → 1-(3,4-Dimethoxyphenyl)-4-((S)-hexahydropyrrolo[1,2-a]pyrazin-2-yl)butane-1,4-dione

Temperature

0 °C

At 0° C., 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (479 mg, 2.5 mmol) was added to a solution of 3-(3,4-dimethoxybenzoyl)propionic acid (596 mg, 2.5 mmol) and 3-hydroxy-3H-dihydrobenzo[d][1,2,3]triazin-4-one (408 mg, 2.5 mmol) in a mixture of dichloromethane (10 ml) and N,N-dimethylformamide (10 ml). The reaction mixture was stirred for 25 min at 0° C. A solution of the crude dihydrochloride salt of (S)-octahydro-pyrrolo[1,2-a]pyrazine in N,N-dimethylformamide (4 ml) and ethyldiisopropylamine (3.0 ml, 17.5 mmol) were added successively. The reaction mixture was stirred for 16 hours, while it was warming up to room temperature. It was diluted with ethyl acetate (200 ml) and washed with a saturated aqueous solution of sodium hydrogen carbonate. The aqueous phase was extracted with ethyl acetate (2×100 ml). The combined organic layers were dried over magnesium sulphate. The solvent was removed in vacuo. The crude product was purified by HPLC on a C18-reversed phase column, using a mixture of 1% trifluoroacetic acid in water and acetonitrile as eluent, to give 148 mg of the title compound.

1. stirringThe reaction mixture was stirred for 16 hours, while it
2. temperaturewas warming up to room temperature
3. washwashed with a saturated aqueous solution of sodium hydrogen carbonate
4. extractionThe aqueous phase was extracted with ethyl acetate (2×100 ml)
5. dry with materialThe combined organic layers were dried over magnesium sulphate
6. customThe solvent was removed in vacuo
7. customThe crude product was purified by HPLC on a C18-reversed phase column
8. additiona mixture of 1% trifluoroacetic acid in water and acetonitrile as eluent

ORD record

ord-c4bdc02b83d74f7e85c03c5bbc83c92a

Source dataset

uspto-grants-2005_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06906060B2