Diisopropylethylamine → 8-Fluoro-11-{3-[2-(4-fluoro-phenyl)-ethyl]-piperazin-1-yl}-2-trifluoromethyl-5H-dibenzo[b,e][1,4]diazepine

HRID 1350535Notes

Reaction equation

HRID 1350535 reaction equation
Cl.[F:2][C:3]1[CH:4]=[CH:5][C:6]2[NH:12][C:11]3[CH:13]=[CH:14][C:15]([C:17]([F:20])([F:19])[F:18])=[CH:16][C:10]=3[C:9]([NH2:21])=[N:8][C:7]=2[CH:22]=1.C(N(C(C)C)CC)(C)C.[F:32][C:33]1[CH:38]=[CH:37][C:36]([CH2:39][CH2:40][CH:41]2[CH2:46]N[CH2:44][CH2:43][NH:42]2)=[CH:35][CH:34]=1>CN1CCCC1=O.C(OCC)(=O)C>[F:2][C:3]1[CH:4]=[CH:5][C:6]2[NH:12][C:11]3[CH:13]=[CH:14][C:15]([C:17]([F:18])([F:20])[F:19])=[CH:16][C:10]=3[C:9]([N:21]3[CH2:44][CH2:43][NH:42][CH:41]([CH2:40][CH2:39][C:36]4[CH:37]=[CH:38][C:33]([F:32])=[CH:34][CH:35]=4)[CH2:46]3)=[N:8][C:7]=2[CH:22]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 178109312-[2-(4-Fluorophenyl)ethyl]piperazineHCID 1357977638-Fluoro-2-trifluoromethyl-5h-dibenzo[b,e][1,4]diazepin-11-ylaminehydrochloride

Product 1

HCID 1357977548-Fluoro-11-{3-[2-(4-fluoro-phenyl)-ethyl]-piperazin-1-yl}-2-trifluoromethyl-5H-dibenzo[b,e][1,4]diazepineYield 28.3%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
195 °C

Procedure

Heat a solution of 8-fluoro-2-trifluoromethyl-5H-dibenzo[b,e][1,4]diazepin-11-ylamine hydrochloride (0.2 g, 0.60 mmol) and diisopropylethylamine (0.086 g, 0.66 mmol) in 1-methyl-2-pyrrolidinone (4 mL) to 60° C. After 30 minutes, add 2-[2-(4-fluoro-phenyl)-ethyl]-piperazine (0.38 g, 1.81 mmol) and heat the reaction mixture to 195° C. for 16 hours. Cool reaction mixture to ambient temperature. Dilute with of ethyl acetate (50 ml) and wash twice with saturated aqueous sodium chloride then twice with water. Collect the organic layer and dry over sodium sulfate. Remove solvent under reduced pressure. Purification via flash chromatography, eluting with a linear gradient starting with 100% dichloromethane and going to 85% of dichloromethane with 15% 2M ammonia in methanol, gives the free base of the title compound (0.083 g, 0.17 mmol, 28% yield) as a yellow amorphous solid: Mass Spectrum (m/e): 487(M+1).

Workup

  1. temperatureCool
  2. customreaction mixture to ambient temperature
  3. washwash twice with saturated aqueous sodium chloride
  4. customCollect the organic layer
  5. dry with materialdry over sodium sulfate
  6. customPurification via flash chromatography
  7. washeluting with a linear gradient

Sources & evidence

ORD record
ord-fa7b3d6dfea540159183632721f50086
Source dataset
uspto-grants-2007_05
Patent number
US07214673B2

Reaction notes

Loading…