Triethylamine → 7,8-Dimethoxy-10-{[2-methyl-2'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl]carbonyl}-[(10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl)carbonyl]-4-piperidinone

HRID 2215132Notes

Reaction equation

HRID 2215132 reaction equation
[CH3:1][O:2][C:3]1[C:4]([O:36][CH3:37])=[CH:5][C:6]2[N:12]([C:13]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[C:27]([F:30])([F:29])[F:28])=[C:17]([CH3:31])[CH:16]=3)=[O:14])[CH2:11][C:10]3=[CH:32][CH:33]=[CH:34][N:9]3[CH2:8][C:7]=2[CH:35]=1.[O:38]=[C:39](Cl)OC(Cl)(Cl)Cl.C(N(CC)CC)C.[NH:53]1[CH2:58][CH2:57][C:56](=[O:59])[CH2:55][CH2:54]1>ClCCl>[CH3:1][O:2][C:3]1[C:4]([O:36][CH3:37])=[CH:5][C:6]2[N:12]([C:13]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[C:27]([F:30])([F:29])[F:28])=[C:17]([CH3:31])[CH:16]=3)=[O:14])[CH2:11][C:10]3=[CH:32][CH:33]=[C:34]([C:39]([N:53]4[CH2:58][CH2:57][C:56](=[O:59])[CH2:55][CH2:54]4)=[O:38])[N:9]3[CH2:8][C:7]=2[CH:35]=1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 10426DiphosgeneHCID 337214-PiperidoneHCID 219477487,8-Dimethoxy-[10,11-dihydro-5H-pyrrolo [2,1-c][1,4]benzodiazepin-10-yl][2-methyl-2'-(trifluoromethyl)[1,1'-biphenyl]-4-yl]methanone

Product 1

HCID 101459497,8-Dimethoxy-10-{[2-methyl-2'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl]carbonyl}-[(10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl)carbonyl]-4-piperidinone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of the 7,8-dimethoxy-[10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl][2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]methanone of Example 12, Step D (0.31 mmol), diphosgene (1.1 equiv.) and triethylamine (1.5 equiv.) in dichloromethane (5 mL) was stirred at room temperature overnight. The solvent was removed in vacuo, the residue was dissolved in dichloromethane (5 mL), and then triethylamine (1.5 equiv.) and 4-piperidone (1.5 equiv.) were added. The reaction mixture was stirred overnight, washed with water, dried over anhydrous magnesium sulfate, filtered and evaporated to dryness. The residue was first chromatographed on silica gel eluting with 2% methanol in dichloromethane and then chromatographed again with 2% methanol in ethyl acetate to provide the title compound as a yellow solid, m.p. 132–134° C.

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue was dissolved in dichloromethane (5 mL)
  3. washwashed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customThe residue was first chromatographed on silica gel eluting with 2% methanol in dichloromethane
  8. customchromatographed again with 2% methanol in ethyl acetate

Sources & evidence

ORD record
ord-2267c93dafbd4fcab5b76a5a1e61ac90
Source dataset
uspto-grants-2006_09
Patent number
US07109193B2

Reaction notes

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