Acetic Acid → HCID 178502268, compound

Participants

Reaction Conditions

Reaction Steps

A solution of (1S,9S)-9-(methoxycarbonylamino)-6,10-dioxooctahydro-1H-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid (184.7 mg, 605 μmol), 4-bromobenzene-1,2-diamine (124 mg, 665 μmol), HATU (230 mg, 605 μmol, Eq: 1.00) in DMF (3 ml) was treated with N,N′-diisopropylethylamine (235 mg, 317 μl, 1.81 mmol, Eq: 3.00). The solution was stirred at 23° C. for 16 h. The reaction mixture was diluted with ethyl acetate, washed with water, brine and dried over MgSO4. The organic layer was concentrated to yield 317.3 mg a 1:1 mixture of [(4S,7S)-4-(2-Amino-4-bromo-phenylcarbamoyl)-6,10-dioxo-octahydro-pyridazino[1,2-a][1,2]diazepin-7-yl]-carbamic acid methyl ester and [(4S,7S)-4-(2-Amino-5-bromo-phenylcarbamoyl)-6,10-dioxo-octahydro-pyridazino[1,2a][1,2]diazepin-7-yl]-carbamic acid methyl ester, as a light brown solid. This mixture was used as such for the next step. A solution of the mixture (317 mg, 508 μmol) in acetic acid (3.12 g, 3 mL, 52.0 mmol) was heated for 1 hr at 90° C. The reaction mixture was cooled to 23° C., and concentrated in vacuo. The residue was dissolved in ethyl acetate (30 mL) washed with sat. NaHCO3, brine and dried (MgSO4). The organic layer was concentrated to yield [(4S,7S)-4-(5-bromo-1H-benzoimidazol-2-yl)-6,10-dioxo-octahydro-pyridazino[1,2-a][1,2]diazepin-7-yl]-carbamic acid methyl ester as light brown powder (191.3 mg, 79.5%). ESI-LRMS m/e calcd for C18H20BrN5O4 [M+] 449. found 450 [M+H1].

Provenance & Evidence