Diisopropylethylamine → 10-[(2',6'-Dimethyl-1,1'-biphenyl-4-yl)carbonyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide

HRID 2244214Notes

Reaction equation

HRID 2244214 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([C:15](Cl)=[O:16])=[CH:11][CH:10]=1.[N:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][NH:25][C:26]([C:28]2[N:37]3[C:31]([CH2:32][NH:33][C:34]4[CH:41]=[CH:40][CH:39]=[CH:38][C:35]=4[CH2:36]3)=[CH:30][CH:29]=2)=[O:27])[CH:19]=1.C(N(CC)C(C)C)(C)C>ClCCl.O1CCCC1>[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([C:15]([N:33]2[C:34]3[CH:41]=[CH:40][CH:39]=[CH:38][C:35]=3[CH2:36][N:37]3[C:28]([C:26]([NH:25][CH2:24][C:20]4[CH:19]=[N:18][CH:23]=[CH:22][CH:21]=4)=[O:27])=[CH:29][CH:30]=[C:31]3[CH2:32]2)=[O:16])=[CH:11][CH:10]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 22053658N-(3-Pyridinylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamideHCID 875406672',6'-Dimethyl-1,1'-biphenyl-4-carboxylic acid chloride

Product 1

HCID 1595160610-[(2',6'-Dimethyl-1,1'-biphenyl-4-yl)carbonyl]-N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamideYield 60.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of 2′,6′-dimethyl-1,1′-biphenyl-4-carboxylic acid of Step A (0.790 g, 3.5 mmol) in dichloromethane (15 mL) was treated under nitrogen with a catalytic amount of N,N-dimethylformamide followed by dropwise addition of 2N oxalyl chloride in dichloromethane (2.8 mL). After the gas evolution ceased the mixture was refluxed for 4 hours, cooled, and evaporated. The residue was azeotroped twice with benzene and dried in vacuo to provide 2′,6′-dimethyl-1,1′-biphenyl-4-carboxylic acid chloride. The crude 2′,6′-dimethyl-1,1′-biphenyl-4-carboxylic acid chloride (0.856 g, 3.5 mmol) was dissolved in dichloromethane (7 mL) and added dropwise to a suspension of N-(pyridin-3-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxamide of Example 12 (0.450 g, 1.41 mmol) in anhydrous tetrahydrofuran 10 mL) containing N,N-diisopropylethyl amine (0.860 mL). The mixture was stirred for 18 hours at room temperature and evaporated to dryness. The residue was dissolved in dichloromethane, the solution washed with saturated aqueous sodium bicarbonate and brine, dried over anhydrous potassium carbonate and evaporated. The residue was chromatographed over silica gel Merck-60 eluting with a gradient from 0 to 4% methanol in 1:1 hexane-ethyl acetate to provide the title compound (0.452 g) as a white solid after trituration with hexane, m.p. 216-218° C. (dec).

Workup

  1. customevaporated to dryness
  2. dissolutionThe residue was dissolved in dichloromethane
  3. washthe solution washed with saturated aqueous sodium bicarbonate and brine
  4. dry with materialdried over anhydrous potassium carbonate
  5. customevaporated
  6. customThe residue was chromatographed over silica gel Merck-60
  7. washeluting with a gradient from 0 to 4% methanol in 1:1 hexane-ethyl acetate

Sources & evidence

ORD record
ord-515961090c14456ba01912764270d7c2
Source dataset
uspto-grants-2010_03
Patent number
US07678787B2

Reaction notes

Loading…