Dimethylformamide → HCID 68185398, compound

Participants

Reaction Steps

A flask was charged with (2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinecarboxylic acid (for a preparation, see Intermediate 63) (100 mg, 0.3 mmol) and HATU (137 mg, 0.360 mmol) then filled with N,N-dimethylformamide (DMF) (2 mL) and DIPEA (0.157 mL, 0.900 mmol). The resulting mixture was stirred at room temperature for 5 min then 1,1-dimethylethyl[2-(hydroxyamino)-2-iminoethyl]carbamate (for a preparation, see Intermediate 67) (68.1 mg, 0.360 mmol) in N,N-dimethylformamide (DMF) (2 mL) was added. The resulting mixture was stirred at this temperature under nitrogen for 30 min, at 110° C. for 7 h then cooled to room temperature. The mixture was partitioned between AcOEt and water and the phases were separated. The aqueous phase was extracted three times with AcOEt and the combined organic were washed twice with water then brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by SP4 using 10 G silica cartridge, (gradient: 8 to 38% (10% MeOH in DCM) in DCM) gave 1-methylethyl((2S,4R)-1-acetyl-6-{3-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]-1,2,4-oxadiazol-5-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate (60 mg, 0.120 mmol, 39.9% yield) as a pale yellow solid. LCMS (method A): Retention time 1.04 min, [M+H-Boc]+=402.0

Provenance & Evidence