Triethylamine → 10-{[6-Chloro-3-methoxy-2'-trifluoromethyl-[1,1'-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine

HRID 2215135Notes

Reaction equation

HRID 2215135 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([OH:10])=O)[C:5]([O:11][CH3:12])=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[C:19]([F:22])([F:21])[F:20].S(Cl)(Cl)=O.[CH:27]1[CH:28]=[CH:29][N:30]2[CH2:36][C:35]3[CH:37]=[CH:38][CH:39]=[CH:40][C:34]=3[NH:33][CH2:32][C:31]=12.C(N(CC)CC)C>O1CCCC1.ClCCl.CN(C)C=O>[Cl:1][C:2]1[C:3]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]([F:20])([F:21])[F:22])=[CH:4][C:5]([O:11][CH3:12])=[C:6]([C:8]([N:33]2[C:34]3[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=3[CH2:36][N:30]3[CH:29]=[CH:28][CH:27]=[C:31]3[CH2:32]2)=[O:10])[CH:7]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 1554704810,11-Dihydro-5H-benzo[e]pyrrolo[1,2-a][1,4]diazepineHCID 219477542-Chloro-5-methoxy-2′-(trifluoromethyl)[1,1′-biphenyl]-4-carboxylic acid

Product 1

HCID 2194779810-{[6-Chloro-3-methoxy-2'-trifluoromethyl-[1,1'-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepineYield 60.4%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A stirred solution of the 2-chloro-2′-trifluoromethyl-5-methoxy[1,1′-biphenyl]-4-carboxylic acid of Step B (3.46 g, 10.46 mmol) in tetrahydrofuran (20 mL) containing a catalytic amount of N,N-dimethylformamide was treated dropwise with thionyl chloride (1.36 g, 11.51 mmol). The reaction mixture was stirred for 2 hours, and then added dropwise to a solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (1.92 g 10.46 mmol) in tetrahydrofuran (20 mL) containing triethylamine (2.32 g, 23 mmol). The reaction mixture was stirred for 2 hours, diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness. Trituration of the residue with acetone gave the title compound (3.14 g). Recrystallization from acetone/hexanes provided white crystals, m.p. 208–210° C.;

Workup

  1. stirringThe reaction mixture was stirred for 2 hours
  2. washwashed with saturated aqueous sodium bicarbonate and brine
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customevaporated to dryness

Sources & evidence

ORD record
ord-a8a0fb771e984a3e84151246ffc206ed
Source dataset
uspto-grants-2006_09
Patent number
US07109193B2

Reaction notes

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