1,3-Bis(benzyloxycarbonyl)-2-methylisothiourea → 1,1-dimethylethyl 7-[2-({[(phenylmethyl)oxy]carbonyl}amino)-1H-benzimidazol-6-yl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate

HRID 473878Notes

Reaction equation

HRID 473878 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:10]=[CH:11][C:12]3[O:18][CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14][C:13]=3[CH:26]=2)[CH:5]=[CH:6][C:7]=1[NH2:8].[CH2:27]([O:34][C:35]([NH:37][C:38](=NC(OCC1C=CC=CC=1)=O)SC)=[O:36])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>C(O)(=O)C>[C:28]1([CH2:27][O:34][C:35]([NH:37][C:38]2[NH:1][C:2]3[CH:3]=[C:4]([C:9]4[CH:10]=[CH:11][C:12]5[O:18][CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:23])([CH3:25])[CH3:24])=[O:20])[CH2:14][C:13]=5[CH:26]=4)[CH:5]=[CH:6][C:7]=3[N:8]=2)=[O:36])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

4

Reactant 2

HCID 46642131,3-Bis(benzyloxycarbonyl)-2-methylisothioureaHCID 668201741,1-dimethylethyl 7-(3,4-diaminophenyl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate

Product 1

HCID 675141291,1-dimethylethyl 7-[2-({[(phenylmethyl)oxy]carbonyl}amino)-1H-benzimidazol-6-yl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylateYield 45.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 1,1-dimethylethyl 7-(3,4-diaminophenyl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (2.0 g, 5.6 mmol) in acetic acid (20 mL) was added 1,3-bis(benzyloxycarbonyl)-2-methyl-2-thiopseudourea (2.4 g, 6.7 mmol) and the resulting mixture was heated (60° C.). After 12 h the reaction mixture was partitioned between ethyl acetate (50 mL) and water (50 mL). The organic layer was then washed with brine (50 mL), dried over anhydrous magnesium sulfate, filtered and concentrated. Column chromatography on silica (0 to 50% ethyl acetate/hexanes) provided 1,1-dimethylethyl 7-[2-({[(phenylmethyl)oxy]carbonyl}amino)-1H-benzimidazol-6-yl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (1.3 g, 45% yield) as a brown solid. MS (EI) for C29H30N4O5: 515 (MH+).

Workup

  1. customAfter 12 h the reaction mixture was partitioned between ethyl acetate (50 mL) and water (50 mL)
  2. washThe organic layer was then washed with brine (50 mL)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-f3abf095759b46bfa0c74951f4593ca9
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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