Diisopropylethylamine → 1-Cyclopropyl-2-(4-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl) piperazin-1-yl)ethane-1,2-dione

4-(4-fluoro-3-(piperazine-1-carbonyl)benzyl)phthalazin-1(2H)-one TFA salt (1.24 g, 2.68 mmol), 2-cyclopropyl-2-oxoacetic acid (2.84 g, 24.84 mmol), DIPEA (6.9 ml, 41.4 mmol), and HATU (4.08 g, 10.8 mmol) were mixed in DMF (100 ml), the resulting reaction mixture was stirred at room temperature for overnight until the reaction finished (monitored by TLC). The reaction mixture was then partitioned between DCM and water (100 ml each, the water phase was extracted with DCM (100 ml). The combined organic phase was washed with water, sat. aqueous sodium bicarbonate, and brine, dried over sodium sulphate, filtered, and concentrated to yield the crude product. Then the crude product was purified by column chromatography on silica gel (DCM: MeOH=100:1) and re-crystallized from methanol to afford the desired product (610 mg, 49.3%) as a white solid.

1. customthe resulting reaction mixture
2. customThe reaction mixture was then partitioned between DCM and water (100 ml each
3. extractionthe water phase was extracted with DCM (100 ml)
4. washThe combined organic phase was washed with water, sat. aqueous sodium bicarbonate, and brine
5. dry with materialdried over sodium sulphate
6. filtrationfiltered
7. concentrationconcentrated
8. customto yield the crude product
9. customThen the crude product was purified by column chromatography on silica gel (DCM: MeOH=100:1)
10. customre-crystallized from methanol

ORDレコード

ord-bc2c7b9cd4ac45e2ab79dde305b07c2b

出典データセット

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08999985B2