Diisopropylethylamine → 10-[(4-Tert-butylphenoxy)acetyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-C][1,4]benzodiazepine-3-carboxamide

To a suspension of N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide of Example 76, Step C (0.300 g, 0.942 mmol), and N,N-diisopropylethylamine (0.26 mL, 1.508 mmol) in dry tetrahydrofuran (10 mL) was added dropwise 4-tert-butylphenoxyacetyl chloride (0.32 g, 1.41 mmol) and the reaction mixture was stirred at room temperature under nitrogen for 21 hours. The reaction was then quenched by the addition of 2 M sodium hydroxide (5 mL) and the mixture partitioned between ethyl acetate (50 mL) and 2 M sodium hydroxide (50 mL). The organic phase was separated, washed with 2 M sodium hydroxide (50 mL), water (50 mL) and brine (50 mL), dried over anhydrous magnesium sulfate, and concentrated in vacuo to afford a yellow foam. Purification by flash chromatography using a solvent gradient of 0 to 4% methanol in dichloromethane gave a colorless syrup that was triturated with diethyl ether to afford the title compound (0.280 g, 58%) as a white solid, m.p. 85° C.

1. customThe reaction was then quenched by the addition of 2 M sodium hydroxide (5 mL)
2. customthe mixture partitioned between ethyl acetate (50 mL) and 2 M sodium hydroxide (50 mL)
3. customThe organic phase was separated
4. washwashed with 2 M sodium hydroxide (50 mL), water (50 mL) and brine (50 mL)
5. dry with materialdried over anhydrous magnesium sulfate
6. concentrationconcentrated in vacuo
7. customto afford a yellow foam
8. customPurification by flash chromatography
9. customgave a colorless syrup that
10. customwas triturated with diethyl ether

ORDレコード

ord-2ea83f27de7c40258ebf87ccedd4bfe9

出典データセット

uspto-grants-2010_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07678787B2