Trichloroacetyl chloride → 2,2,2-trichloro-1-[10-(2'-methoxy-2-methyl-biphenyl-4-carbonyl)-10,11-dihydro-5H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-3-yl]-ethanone

HRID 639267Notes

Reaction equation

HRID 639267 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[O:29][CH3:30])=[C:19]([CH3:31])[CH:18]=3)=[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[O:29][CH3:30])=[C:19]([CH3:31])[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:44]

Participants

5

Reactant 3

HCID 6420Trichloroacetyl chlorideHCID 81531DiisopropylethylamineHCID 21947842(10,11-Dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-(2'-methoxy-2-methyl-[1,1'-biphenyl]-4-yl)-methanone

Product 1

HCID 219479472,2,2-trichloro-1-[10-(2'-methoxy-2-methyl-biphenyl-4-carbonyl)-10,11-dihydro-5H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-3-yl]-ethanoneYield 103.3%

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′-methoxy-2-methyl-[1,1′-biphenyl]-4-yl)-methanone of Step C (1.5 g, 3.67 mmol) in dichloromethane (20 mL) was added N,N-diisopropylethylamine (1.28 mL, 7.35 mmol) followed by slow addition of trichloroacetyl chloride (1.23 mL, 11.0 mmol). The reaction mixture was stirred overnight at room temperature then 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 provided 2.1 g of title compound. The material was redissolved in dichloromethane and evaporated to dryness to provide a yellow foam, which was used in the next step. MS [(+)APCI, m/z]: 553 [M+H]+ Anal. Calcd. for C29H23Cl3N2O3+0.13 C4H8O2+0.13 CH2Cl2:C, 61.79; H, 4.25; N, 4.86. Found: C, 60.43; H, 4.50; N, 4.80.

Workup

  1. customthen 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-2e4c56f949234035975c1c3758b4c973
Source dataset
uspto-grants-2010_04
Patent number
US07691848B2

Reaction notes

Loading…