Triethylamine → 10-[(2-Methoxy-2'-methyl-1,1'-biphenyl-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine

HRID 639236Notes

Reaction equation

HRID 639236 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([OH:11])=O)[CH:6]=[CH:5][C:4]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[CH3:18].C(Cl)(=O)C(Cl)=O.[CH:25]1[CH:26]=[CH:27][N:28]2[CH2:34][C:33]3[CH:35]=[CH:36][CH:37]=[CH:38][C:32]=3[NH:31][CH2:30][C:29]=12.C(N(CC)CC)C>ClCCl.CN(C)C=O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([N:31]2[C:32]3[CH:38]=[CH:37][CH:36]=[CH:35][C:33]=3[CH2:34][N:28]3[CH:27]=[CH:26][CH:25]=[C:29]3[CH2:30]2)=[O:11])[CH:6]=[CH:5][C:4]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[CH3:18]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 1554704810,11-Dihydro-5H-benzo[e]pyrrolo[1,2-a][1,4]diazepineHCID 180010763-Methoxy-4-(2-methylphenyl)benzoic acid

Product 1

HCID 6867947010-[(2-Methoxy-2'-methyl-1,1'-biphenyl-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepineYield 95%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-methoxy-2′-methyl-biphenyl-4-carboxylic acid of step D (23 mmol) in dichloromethane (50 mL) was added a drop of N,N-dimethylformamide. Oxalyl chloride (36 mmol) then was added dropwise to the solution, which then was stirred at reflux temperature for 2 hours. The solvents were evaporated and the resulting acid chloride was dissolved in 20 mL dichloromethane. This was added dropwise to a stirred mixture of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (25 mmol) and triethylamine (34 mmol) in dichloromethane (30 mL) at 0° C. under nitrogen atmosphere. After 20 hours the mixture was quenched with water and washed with 0.5 N hydrochloric acid, 1.0 N sodium hydroxide, and brine. The solution was dried over anhydrous sodium sulfate, and evaporated to a solid. The product was purified by flash chromatography using ethyl acetate/hexane (1:3) to yield 8.77 g (95%) of the title compound as a white solid.

Workup

  1. temperatureat reflux temperature for 2 hours
  2. customThe solvents were evaporated
  3. dissolutionthe resulting acid chloride was dissolved in 20 mL dichloromethane
  4. customAfter 20 hours the mixture was quenched with water
  5. washwashed with 0.5 N hydrochloric acid, 1.0 N sodium hydroxide, and brine
  6. dry with materialThe solution was dried over anhydrous sodium sulfate
  7. customevaporated to a solid
  8. customThe product was purified by flash chromatography

Sources & evidence

ORD record
ord-2a3c698a75924f2ab01f36e4fbd4d7f8
Source dataset
uspto-grants-2010_04
Patent number
US07691848B2

Reaction notes

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