Benzoyl chloride → (1S, 9S) t-Butyl 9-benzoylamino-6,10-dioxo-1,2,3,4,7,8,9,10-octahydro-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxylate

HRID 2230437Notes

Reaction equation

HRID 2230437 reaction equation
[C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:10][C@@H:11]1[C:17](=[O:18])[N:16]2[C@H:19]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:20][CH2:21][CH2:22][N:15]2[C:14](=[O:30])[CH2:13][CH2:12]1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[C:1]([NH:10][C@@H:11]1[C:17](=[O:18])[N:16]2[C@H:19]([C:23]([O:25][C:26]([CH3:28])([CH3:27])[CH3:29])=[O:24])[CH2:20][CH2:21][CH2:22][N:15]2[C:14](=[O:30])[CH2:13][CH2:12]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 7412Benzoyl chlorideHCID 81531DiisopropylethylamineHCID 15434568tert-Butyl (1S,9S)-9-amino-6,10-dioxooctahydro-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxylate

Product 1

HCID 57166602(1S, 9S) t-Butyl 9-benzoylamino-6,10-dioxo-1,2,3,4,7,8,9,10-octahydro-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxylateYield 95.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of benzoyl chloride (1.61 g, 11.47 mmol) in CH2Cl2 (15 ml) was added dropwise to a stirred ice cold mixture of (1S,9S) t-butyl 9-amino-6,10-dioxo-1,2,3,4,7,8,9,10-octahydro-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxylate (GB 2,128,984; 3.1 g, 10.43 mmol), dry CH2Cl2 (20 ml) and diisopropylethylamine (4.54 ml, 26.06 mmol). The mixture was kept cold for 1 h then left at room temperature for 0.5 h. The mixture was diluted with CH2Cl2, washed twice with brine, dried (MgSO4) and concentrated. The residue was purified by flash chromatography (0-5% methanol in CH2Cl2) to afford 211e (4.0 g, 95%) of a colourless glass: mp 74-76° C.; [α]D30 −75.0° (c 0.12, CH2Cl2). IR (KBr) 3350, 2979, 2938, 1736, 1677, 1662, 1536, 1422, 1276, 1250, 1155; 1H NMR (CDCl3) δ8.72 (2H, m), 7.53-7.40 (3H, m), 7.07 (1H, d, J=7.2), 5.30 (1H, dd, J=3.0, 5.8), 5.12 (1H, m), 4.66 (1H, m), 3.51 (1H, m), 2.90 (2H, m), 2.38 (1H, dd, J=13.2, 6.8), 2.25 (1H, m), 1.9 (2H, m), 1.70 (1H, m). Anal. Calcd for C21H27N3O50.5H2O: C, 61.45; H, 6.88; N, 10.24. Found C, 61.69; H, 6.71; N, 10.18.

Workup

  1. waitthen left at room temperature for 0.5 h
  2. washwashed twice with brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography (0-5% methanol in CH2Cl2)

Sources & evidence

ORD record
ord-e1b94d019eaa432c8bcaaff6daa95665
Source dataset
uspto-grants-2002_07
Patent number
US06423840B1

Reaction notes

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