Diisopropylethylamine → benzyl (4S,7S)-4-(2-(4-bromophenyl)-2-oxoethylcarbamoyl)-6,10-dioxooctahydro-1H-pyridazino[1,2-a][1,2]diazepin-7-ylcarbamate

In a 50 ml, round-bottomed flask, (1S,9S)-9-(benzyloxycarbonylamino)-6,10-dioxo octahydro-1H-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid (1 g, 2.66 mmol) was combined with DMF (15 ml) to give a colorless solution. HATU (1.01 g, 2.66 mmol) was added and stirred at room temperature for 10 min. 2-Amino-1-(4-bromophenyl)ethanone HCl (666 mg, 2.66 mmol, Eq: 1.00) and DIPEA (1.03 g, 1.4 ml, 7.99 mmol) were added and stirred at room temperature overnight. The reaction mixture was diluted with brine and H2O and extracted with EtOAc (2×60 ml). The organic layers were combined, washed with brine (2×20 mL), H2O (2×50 mL), dried with MgSO4 and concentrated in vacuo. The crude product was purified on a silica gel column (CH2Cl2, 2%, 3%, 5%, 6%, 8% MeOH/CH2Cl2) to afford benzyl (4S,7S)-4-(2-(4-bromophenyl)-2-oxoethylcarbamoyl)-6,10-dioxooctahydro-1H-pyridazino[1,2-a][1,2]diazepin-7-ylcarbamate as a light yellow solid (1.2 g, 78.8%). ESI-LRMS m/e calcd for C26H27BrN4O6 [M+] 571. found 572 [M+H+].

1. customto give a colorless solution
2. stirringstirred at room temperature overnight
3. extractionextracted with EtOAc (2×60 ml)
4. washwashed with brine (2×20 mL), H2O (2×50 mL)
5. dry with materialdried with MgSO4
6. concentrationconcentrated in vacuo
7. customThe crude product was purified on a silica gel column (CH2Cl2, 2%, 3%, 5%, 6%, 8% MeOH/CH2Cl2)

ORD 기록

ord-e220c39edd1f42ca9a0e100380fdfa14

출처 데이터셋

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09180193B2