Methyl [[(methoxycarbonyl)amino](methylthio)methylene]carbamate → 1,1-dimethylethyl 7-(2-{[(methyloxy)carbonyl]amino}-1H-benzimidazol-6-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate

HRID 473867Notes

Reaction equation

HRID 473867 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[O:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13][C:12]=3[CH:25]=2)=[CH:4][C:3]=1[N+:26]([O-])=O.[CH3:29][O:30][C:31]([NH:33][C:34](=NC(OC)=O)SC)=[O:32]>[Pd].C(O)C>[CH3:29][O:30][C:31]([NH:33][C:34]1[NH:26][C:3]2[CH:4]=[C:5]([C:8]3[CH:9]=[CH:10][C:11]4[O:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13][C:12]=4[CH:25]=3)[CH:6]=[CH:7][C:2]=2[N:1]=1)=[O:32]

Participants

5

Reactant 2

HCID 98708Methyl [[(methoxycarbonyl)amino](methylthio)methylene]carbamateHCID 675056591,1-dimethylethyl 7-(4-amino-3-nitrophenyl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate

Product 1

HCID 675150971,1-dimethylethyl 7-(2-{[(methyloxy)carbonyl]amino}-1H-benzimidazol-6-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylateYield 80%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

1,1-Dimethylethyl 7-(4-amino-3-nitrophenyl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (3.3 g, 8.56 mmol) and 10% palladium on carbon (300 mg) were suspended in ethanol (100 mL) and the mixture was hydrogenated at 50 psi using a Parr apparatus for 12 h. The mixture was filtered through a celite pad and the filtrate concentrated. The residue was taken into acetic acid (25 mL) followed by addition of 1,3-bis(methoxycarbonyl)-2-methyl-2-thiopseudourea (2.3 g, 11.15 mmol) and the resulting mixture heated to 80° C. for 30 minutes. The mixture was cooled to room temperature then concentrated and partitioned with ethyl ether (60 mL) and dilute aqueous sodium bicarbonate. The biphasic mixture was allowed to stand for several minutes until a precipitate formed. The solid was collected by filtration, washed with water then ethyl ether and dried to give 1,1-dimethylethyl 7-(2-{[(methyloxy)carbonyl]amino}-1H-benzimidazol-6-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (2.98 g, 80% yield) as a white solid. MS (EI) for C23H26N4O5: 439 (MH+).

Workup

  1. customfor 12 h
  2. filtrationThe mixture was filtered through a celite pad
  3. concentrationthe filtrate concentrated
  4. temperatureThe mixture was cooled to room temperature
  5. concentrationthen concentrated
  6. custompartitioned with ethyl ether (60 mL) and dilute aqueous sodium bicarbonate
  7. waitto stand for several minutes until a precipitate
  8. customformed
  9. filtrationThe solid was collected by filtration
  10. washwashed with water
  11. dry with materialethyl ether and dried

Sources & evidence

ORD record
ord-b6d8cbfd81484e318191fed4c53dbfe2
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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