Dimethylamine, hydrochloride → HCID 69287820, compound

Participants

Reaction Steps

The compound 3-nitro-5-trifluoromethylbenzoic acid (500 mg, 2.1 mmol) was dissolved in 20 mL of 1:1 CH2Cl2/DMF. The resultant solution was charged sequentially with dimethylamine hydrochloride (174 mg, 2.1 mmol), N,N-diisopropylethylamine (3.7 mL, 21 mmol) and HATU (970 mg, 2.6 mmol). The mixture was stirred for 12 h at RT, concentrated in vacuo, and partitioned between EtOAc and sat. NH4Cl. The aqueous phase was extracted with EtOAc (1×). The combined organic extracts were washed with sat. NaHCO3 and brine, dried (Na2SO4), filtered, and concentrated in vacuo. A portion (107 mg) of this product was dissolved in MeOH (6 mL). This solution was charged with 5% Pd/C, Degussa style (21 mg), stirred under H2 (1 atm) for 12 h at RT, filtered, and concentrated in vacuo. The residue was dissolved in 6 mL of 1:1 CH2Cl2/DMF. The resultant solution was charged sequentially with the lithium salt of N-[(1S,2S)-1-(benzyloxycarbonylamino-methyl)-2-hydroxy-pent-3-ynyl]-malonamic acid (141 mg, 0.4 mmol, see procedure 21a), N, N-diisopropylethylamine (0.35 mL, 2.0 mmol) and HATU (182 mg, 0.5 mmol). The mixture was stirred for 12 h at RT, concentrated in vacuo, and partitioned between EtOAc and sat. NH4Cl. The aqueous phase was extracted with EtOAc (1×). The combined organic extracts were washed with sat. NaHCO3 and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography to afford {(2S,3S)-2-[2-(3-dimethylcarbamoyl-5-trifluoromethyl-phenylcarbamoyl)-acetylamino]-3-hydroxy-hex-4-ynyl}-carbamic acid benzyl ester as a colorless oil (186 mg, 81% yield). MS found: (M+Na)+=585.3.

Provenance & Evidence