Diisopropylethylamine → HCID 68187784, 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 the mixture was treated with 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 64) (68.1 mg, 0.360 mmol) in N,N-dimethylformamide (DMF) (2 mL) was added. The resulting mixture was stirred at room 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 phases were washed twice with water then brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by SP4 using a 10 G silica cartridge (gradient: 8 to 38% (10% MeOH in DCM) in DCM) gave 1-methylethyl((2S,4R)-1-acetyl-6-{3-[({[(1,1-dimethylethyl)oxy]carbonyl}amino)methyl]-1,2,4-oxadiazol-5-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate (70 mg, 0.144 mmol, 47.9% yield) as a pale yellow solid.

Provenance & Evidence