Water → Ethyl 10-(((dimethylamino)(oxo)acetyl)amino)-4-oxo-3-((phenylcarbonyl)oxy)-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylate

HRID 1093080Notes

Reaction equation

HRID 1093080 reaction equation
Cl.[NH2:2][C:3]12[CH2:11][CH2:10][CH:7]([CH2:8][CH2:9]1)[CH2:6][N:5]1[C:12](=[O:30])[C:13]([O:21][C:22]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[O:23])=[C:14]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[N:15]=[C:4]21.[CH3:31][N:32]([CH3:38])[C:33](=[O:37])[C:34](O)=[O:35].C(N(C(C)C)CC)(C)C.O>CN(C=O)C>[CH3:31][N:32]([C:33](=[O:37])[C:34]([NH:2][C:3]12[CH2:11][CH2:10][CH:7]([CH2:8][CH2:9]1)[CH2:6][N:5]1[C:12](=[O:30])[C:13]([O:21][C:22]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)=[O:23])=[C:14]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[N:15]=[C:4]21)=[O:35])[CH3:38]

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 2760995N,N-Dimethyloxamic acidHCID 66588778Ethyl 10-amino-4-oxo-3-((phenylcarbonyl)oxy)-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylate hydrochloride

Product 1

HCID 66588776Ethyl 10-(((dimethylamino)(oxo)acetyl)amino)-4-oxo-3-((phenylcarbonyl)oxy)-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylateYield 91.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of ethyl 10-amino-4-oxo-3-((phenylcarbonyl)oxy)-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylate hydrochloride (2.4 g, 5.53 mmol) in DMF (50 mL) as added 2-(dimethylamino)-2-oxoacetic acid (1.295 g, 11.06 mmol), diisopropyl-ethylamine (5.80 mL, 33.2 mmol) and the resulting mixture was stirred at room temperature for 3 h. Water was then added and the mixture extracted with ethyl acetate (2×200 mL). The organic solution was washed with 1N HCl (50 mL), dried (Na2SO4), filtered and concentrated. The crude material was triturated with ethyl acetate/hexane to afford the title compound (2.5 g, 5.04 mmol, 91% yield) as a light yellow solid. 1H NMR (500 MHz, CDCl3) δ: 9.33 (1 H, brs), 8.18 (2 H, d, J=7.02 Hz), 7.64 (1 H, t, J=7.48 Hz), 7.50 (2 H, t, J=7.93 Hz), 4.29 (2 H, q, J=7.02 Hz), 4.17 (2 H, d, J=3.66 Hz), 3.34 (3 H, s), 3.03 (3 H, s), 2.88-3.00 (2 H, m), 2.50 (1 H, brs), 1.93-2.10 (4 H, m), 1.73-1.82 (2 H, m), 1.18 (3 H, t, J=7.17 Hz). LCMS (M+H)=497.79.

Workup

  1. extractionthe mixture extracted with ethyl acetate (2×200 mL)
  2. washThe organic solution was washed with 1N HCl (50 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was triturated with ethyl acetate/hexane

Sources & evidence

ORD record
ord-d795e993b573435bb645218cf4264c49
Source dataset
uspto-grants-2012_03
Patent number
US08129398B2

Reaction notes

Loading…