Trichloroacetyl chloride → 2,2,2-Trichloro-1-{10-[(3-methoxy-2'-methyl-[1,1'-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}ethanone

HRID 1830080Notes

Reaction equation

HRID 1830080 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])=[CH:19][C:18]=3[O:30][CH3:31])=[O:16])[CH2:6][C:5]=12.C(N(CC)C(C)C)(C)C.[Cl:41][C:42]([Cl:47])([Cl:46])[C:43](Cl)=[O:44]>ClCCl>[Cl:41][C:42]([Cl:47])([Cl:46])[C:43]([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])=[CH:19][C:18]=3[O:30][CH3:31])=[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:44]

Participants

5

Reactant 3

HCID 6420Trichloroacetyl chlorideHCID 81531DiisopropylethylamineHCID 21947713(10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-[3-methoxy-2'-methyl-[1,1'-biphenyl]-4-yl]-methanone

Product 1

HCID 219478752,2,2-Trichloro-1-{10-[(3-methoxy-2'-methyl-[1,1'-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}ethanoneYield 92.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-[3-methoxy-2′-methyl-[1,1′-biphenyl]-4-yl]-methanone of Step D (1.36 g, 3.33 mmol) in dichloromethane (15 mL) was added N,N-diisopropylethyl amine (1.2 mL, 6.89 mmol) followed by slow addition of trichloroacetyl chloride (1.1 mL, 9.85 mmol). The reaction mixture was stirred overnight at room temperature then was quenched with water. The organic phase was washed with 0.1 N hydrochloric acid followed by water, then dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a green oil. Purification by flash chromatography on silica gel using a solvent system of 20% ethyl acetate in hexane gave 1.7 g of title product as a yellow foam.

Workup

  1. customthen was quenched with water
  2. washThe organic phase was washed with 0.1 N hydrochloric acid
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give a green oil
  7. customPurification by flash chromatography on silica gel using a solvent system of 20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-c5670b4317054a19a872ed9387204969
Source dataset
uspto-grants-2006_06
Patent number
US07064120B2

Reaction notes

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