Methyl Isocyanate → N-[1-[[2'-[(Methylaminocarbonyl)oxy][1,1'-biphenyl]-4-yl]methyl]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]-3-t-butoxycarbonylamino-3-methylbutanamide

HRID 1974607Notes

Reaction equation

HRID 1974607 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][C:11]([CH2:14][N:15]2[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[CH2:19][CH2:18][C@@H:17]([NH:26][C:27](=[O:40])[CH2:28][C:29]([NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])([CH3:31])[CH3:30])[C:16]2=[O:41])=[CH:10][CH:9]=1.[CH3:42][N:43]=[C:44]=[O:45].N12CCCN=C1CCCCC2>C(Cl)Cl>[CH3:42][NH:43][C:44]([O:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:9]=[CH:10][C:11]([CH2:14][N:15]2[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[CH2:19][CH2:18][C@@H:17]([NH:26][C:27](=[O:40])[CH2:28][C:29]([NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])([CH3:31])[CH3:30])[C:16]2=[O:41])=[CH:12][CH:13]=1)=[O:45]

Participants

5

Reactant 3

HCID 12228Methyl IsocyanateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 22850220N-[1-[[(2'-Hydroxy)[1,1'-biphenyl]-4-yl]methyl]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]-3-t-butoxycarbonylamino-3-methylbutanamide

Product 1

HCID 22850227N-[1-[[2'-[(Methylaminocarbonyl)oxy][1,1'-biphenyl]-4-yl]methyl]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]-3-t-butoxycarbonylamino-3-methylbutanamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 100 mg (approx. 0.2 mmol) of the crude intermediate obtained in Step G in 5 mL of methylene chloride was treated with 1.0 mL of methyl isocyanate (17 mmol) and 0.1 mL of 1,8-diazabicyclo[5.4.0]undec-7-ene under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 10 minutes and then evaporated under vacuum to give 146 mg ofo crude product. 1H NMR (400 MHz, CDCl3): 1.32 (s, 3H), 1.33 (s, 3H), 1.39 (s, 9H), 2.12 (m, 1H), 2.33 (m, 1H), 2.52 (dd, 1H), 2.57 (m, 2H), 2.59 (s, 3H), 4.38 (dd, 1H), 4.8 (d, 1H), 5.26 (d, 1H), 7.10 (d, 1H), 7.36 (m, 11H).

Workup

  1. customevaporated under vacuum
  2. customto give 146 mg ofo crude product

Sources & evidence

ORD record
ord-77dba9f03bca44029428afcead8ec28d
Source dataset
uspto-grants-1994_02
Patent number
US05283241

Reaction notes

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