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

HRID 1711949Notes

Reaction equation

HRID 1711949 reaction equation
[C:1](OC(=O)C)(=[O:3])[CH3:2].[NH2:8][CH:9]1[C:15](=[O:16])[N:14]2[CH:17]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:18][CH2:19][CH2:20][N:13]2[C:12](=[O:28])[CH2:11][CH2:10]1.C(N(C(C)C)CC)(C)C.C(Cl)Cl>CCOC(C)=O>[C:1]([NH:8][C@@H:9]1[C:15](=[O:16])[N:14]2[C@H:17]([C:21]([O:23][C:24]([CH3:25])([CH3:27])[CH3:26])=[O:22])[CH2:18][CH2:19][CH2:20][N:13]2[C:12](=[O:28])[CH2:11][CH2:10]1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 11174000HCID 11174000, compound

Product 1

HCID 57306730(1S, 9S) t-Butyl 9-acetylamino-6,10-dioxo-1,2,3,4,7,8,9,10-octahydro-6H-pyridazino [1,2-a][1,2]diazepine-1-carboxylateYield 86.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Acetic anhydride (307 mg, 3.01 mmol) was added to a stirred mixture of 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; 813.7 mg, 2.74 mmol), diisopropylethylamine (884 mg, 6.84 mmol) and CH2Cl2 (20 ml). The mixture was kept for 1 h then diluted with EtOAc, washed with NaHCO3 solution then brine, dried (MgSO4) and concentrated to yield a colourless oil. The product was purified by flash chromatography (0.5-8% MeOH/CH2Cl2) to afford 211c (804 mg, 71%) of colourless powder: mp 162-3° C.; [α]D23−109 (c 1.03, CH2Cl2); IR (KBr) 3358, 2974, 1733, 1693, 1668, 1528, 1462, 1431, 1406, 1371, 1278, 1271, 1250, 1233, 1217, 1154, 1124; 6H NMR (CDCl3) δ 6.32 (1H, d), 5.29-5.25 (1H, m), 4.98-4.85 (1H, m), 4.68-4.58 (1H, m), 3.55-3.39 (1H, m), 2.91-2.66 (2H, m), 2.39-2.18 (2H, m), 2.03 (3H, s), 1.88-1.64 (4H, m), 1.47 (9H, s); Anal. Calcd for C16H25N3O5: C, 56.62; H, 7.43; N, 12.38. Found: C, 56.62; H, 7.43; N, 12.36. MS (+FAB) 340 (M++1, 40%), 284 (100).

Workup

  1. washwashed with NaHCO3 solution
  2. dry with materialbrine, dried (MgSO4)
  3. concentrationconcentrated
  4. customto yield a colourless oil
  5. customThe product was purified by flash chromatography (0.5-8% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-61135757b69746bd978af560fa72584b
Source dataset
uspto-grants-2010_09
Patent number
US07790713B2

Reaction notes

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