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 1830058Notes

Reaction equation

HRID 1830058 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 3.14 g of the title compound. Recrystallization from acetone/hexane 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-9e20fffa23a147848fb8287b2caa06af
Source dataset
uspto-grants-2006_06
Patent number
US07064120B2

Reaction notes

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