Hydrochloric Acid → 4-Amino-N-{[1-(4-chlorophenyl)cyclopropyl]methyl}-3-fluorobenzamide

To a mixture of 4-amino-3-fluorobenzoic acid (180.0 mg, 1.160 mmol) and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (HATU, 0.44 g, 1.2 mmol) in N,N-dimethylformamide (2 mL, 20 mmol) at 0° C. were added N,N-diisopropylethylamine (0.61 mL, 3.5 mmol) and C-[1-(4-chloro-phenyl)-cyclopropyl]-methylamine; hydrochloride (303.7 mg, 1.392 mmol). The reaction mixture was slowly warmed to rt. The reaction mixture was quenched with an equal volume of saturated aqueous sodium bicarbonate and extracted with ethyl acetate (3×). The combined organic layers were washed successively with water, aqueous lithium chloride, and brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified on the Isco (120 g cartridge, chloroform to 12% methanol in chloroform).

1. customThe reaction mixture was quenched with an equal volume of saturated aqueous sodium bicarbonate
2. extractionextracted with ethyl acetate (3×)
3. washThe combined organic layers were washed successively with water, aqueous lithium chloride, and brine
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified on the Isco (120 g cartridge, chloroform to 12% methanol in chloroform)

ORDレコード

ord-0af4449e5f6b4adfaac378c292602afd

出典データセット

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08357711B2