Thionyl Chloride → (10,11-Dihydro-5H-pyrrolo[2,1-c][1,4] benzodiazepin-10-yl)-(2-methoxy-2'-trifluoromethyl-[1,1'-biphenyl]-4-yl)-methanone

HRID 2215144Notes

Reaction equation

HRID 2215144 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9](O)=[O:10])[CH:6]=[CH:5][C:4]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:18]([F:21])([F:20])[F:19].S(Cl)(Cl)=O.[CH:26]1[CH:27]=[CH:28][N:29]2[CH2:35][C:34]3[CH:36]=[CH:37][CH:38]=[CH:39][C:33]=3[NH:32][CH2:31][C:30]=12.C(N(CC)C(C)C)(C)C>CN(C)C=O.C1(C)C=CC=CC=1>[CH:26]1[CH:27]=[CH:28][N:29]2[CH2:35][C:34]3[CH:36]=[CH:37][CH:38]=[CH:39][C:33]=3[N:32]([C:9]([C:7]3[CH:6]=[CH:5][C:4]([C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=4[C:18]([F:21])([F:20])[F:19])=[C:3]([O:2][CH3:1])[CH:8]=3)=[O:10])[CH2:31][C:30]=12

Participants

7

Reactant 4

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 1554704810,11-Dihydro-5H-benzo[e]pyrrolo[1,2-a][1,4]diazepineHCID 219477213-Methoxy-4-(2-trifluoromethylphenyl)benzoic acid

Product 1

HCID 21947785(10,11-Dihydro-5H-pyrrolo[2,1-c][1,4] benzodiazepin-10-yl)-(2-methoxy-2'-trifluoromethyl-[1,1'-biphenyl]-4-yl)-methanoneYield 50.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

The 2-methoxy-2′-trifluoromethyl-[1,1′-biphenyl]-4-carboxylic acid of step C (1.6 g, 5.40 mmol) was added to a flask containing toluene (30 mL), thionyl chloride (1.4 mL) and one drop of N,N-dimethylformamide. The solution was stirred at 70° C. for 1 hour and then concentrated in vacuo. The residue was diluted with dichloromethane (40 mL) and to this solution was added 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (0.94 9, 5.16 mmol). After the solution became homogeneous, N,N-diisopropylethyl amine (1.07 mL, 6.19 mmol) was added in one portion at 0° C. After 30 minutes the solution was concentrated, and the residue partitioned between water and ethyl acetate. The ethyl acetate was dried and concentrated to give a crude oil, which was chromatographed on silica gel eluting with 30% ethyl acetate in hexane to yield 1.2 g of product. The solid was recrystallized from ethyl acetate/hexane to provide the desired title product (0.87 g) as colorless crystals, m.p. 146–148° C.

Workup

  1. concentrationconcentrated in vacuo
  2. additionThe residue was diluted with dichloromethane (40 mL) and to this solution
  3. concentrationAfter 30 minutes the solution was concentrated
  4. customthe residue partitioned between water and ethyl acetate
  5. dry with materialThe ethyl acetate was dried
  6. concentrationconcentrated
  7. customto give a crude oil, which
  8. customwas chromatographed on silica gel eluting with 30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-bc003126b82140988bd09e847365f3d9
Source dataset
uspto-grants-2006_09
Patent number
US07109193B2

Reaction notes

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