N,N-Dimethylaniline → 2,2,2-Trichloro-1-{10-[(2,2'-dimethyl-1,1'-biphenyl-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}ethanone

HRID 639209Notes

Reaction equation

HRID 639209 reaction equation
[CH:1]1[CH:2]=[CH:3][N:4]2[CH2:10][C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[N:7]([C:15]([C:17]3[CH:22]=[CH:21][C:20]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[CH3:29])=[C:19]([CH3:30])[CH:18]=3)=[O:16])[CH2:6][C:5]=12.CN(C)C1C=CC=CC=1.[Cl:40][C:41]([Cl:46])([Cl:45])[C:42](Cl)=[O:43]>ClCCl>[Cl:40][C:41]([Cl:46])([Cl:45])[C:42]([C:3]1[N:4]2[C:5]([CH2:6][N:7]([C:15]([C:17]3[CH:22]=[CH:21][C:20]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[CH3:29])=[C:19]([CH3:30])[CH:18]=3)=[O:16])[C:8]3[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=3[CH2:10]2)=[CH:1][CH:2]=1)=[O:43]

Participants

5

Reactant 3

HCID 949N,N-DimethylanilineHCID 6420Trichloroacetyl chlorideHCID 68680291(10,11-Dihydro-5H-pyrrolo[2,1-c](1,4]benzodiazepin-10-yl)-(2,2'-dimethyl-biphenyl-4-yl)-methanone

Product 1

HCID 160384712,2,2-Trichloro-1-{10-[(2,2'-dimethyl-1,1'-biphenyl-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}ethanoneYield 94%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-(2,2′-dimethyl-biphenyl-4-yl)-methanone of Step C (12.4 g, 31.6 mmol) and N,N-dimethylaniline (6.4 mL, 50.5 mmol) in dry dichloromethane (90 mL) at 0° C. under nitrogen, was added trichloroacetyl chloride (5.3 mL, 47.5 mmol). The reaction was then allowed to warm slowly to room temperature while stirring overnight. The reaction mixture then was washed with 2N hydrochloric acid (2×100 mL), water (100 mL) and brine (100 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give a dark foam. Purification by filtration through a plug of silica gel (60 g) eluting with dichloromethane afforded the title compound (15.9 g, 94%) as a light orange solid, m.p. 212-214° C. MS [(+)ESI, m/z]: 537 [M+H]+.

Workup

  1. washThe reaction mixture then was washed with 2N hydrochloric acid (2×100 mL), water (100 mL) and brine (100 mL)
  2. dry with materialdried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give a dark foam
  6. customPurification
  7. filtrationby filtration through a plug of silica gel (60 g)
  8. washeluting with dichloromethane

Sources & evidence

ORD record
ord-b5f34901c7c44f618805f3af9a718e8e
Source dataset
uspto-grants-2010_04
Patent number
US07691848B2

Reaction notes

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