Triethylamine → N-(4-acetyl-2,6-dichlorophenyl)-3-(aminocarbonyl)-4-[5,5-bis(4-fluorophenyl)pentyl]-1-piperazineacetamide dihydrochloride

HRID 1073186Notes

Reaction equation

HRID 1073186 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][CH:6]([C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)[C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=1.[C:21]([C:24]1[CH:29]=[C:28]([Cl:30])[C:27]([NH:31][C:32](=[O:43])[CH2:33][N:34]2[CH2:39][CH2:38][NH:37][CH:36]([C:40]([NH2:42])=[O:41])[CH2:35]2)=[C:26]([Cl:44])[CH:25]=1)(=[O:23])[CH3:22].C(N(CC)CC)C>CN(C)C=O>[ClH:30].[ClH:30].[C:21]([C:24]1[CH:29]=[C:28]([Cl:30])[C:27]([NH:31][C:32](=[O:43])[CH2:33][N:34]2[CH2:39][CH2:38][N:37]([CH2:2][CH2:3][CH2:4][CH2:5][CH:6]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)[C:7]3[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=3)[CH:36]([C:40]([NH2:42])=[O:41])[CH2:35]2)=[C:26]([Cl:44])[CH:25]=1)(=[O:23])[CH3:22]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 111105561,1'-(5-Bromo-1-pentylidene)bis[4-fluorobenzene]HCID 14722538N-(4-acetyl-2,6-dichlorophenyl)-3-(aminocarbonyl)-1-piperazineacetamide

Product 1

HCID 22373104N-(4-acetyl-2,6-dichlorophenyl)-3-(aminocarbonyl)-4-[5,5-bis(4-fluorophenyl)pentyl]-1-piperazineacetamide dihydrochlorideYield 24%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 5.9 parts of 1,1'-(5-bromo-1-pentylidene)bis[4-fluorobenzene], 5.6 parts of N-(4-acetyl-2,6-dichlorophenyl)-3-(aminocarbonyl)-1-piperazineacetamide, 4.05 parts of N,N-diethylethanamine and 90 parts of N,N-dimethylformamide was stirred over weekend at 70° C. After evaporation, the residue was taken up in dichloromethane. The organic layer was washed with water, dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (97:3 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was converted into the hydrochloride salt in acetonitrile and 2-propanol. The salt was filtered off and dried, yielding 2.54 parts (24.0%) of N-(4-acetyl-2,6-dichlorophenyl)-3-(aminocarbonyl)-4-[5,5-bis(4-fluorophenyl)pentyl]-1-piperazineacetamide dihydrochloride; mp. 181.2° C. (compound 14).

Workup

  1. customAfter evaporation
  2. washThe organic layer was washed with water
  3. customdried
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by column chromatography over silica gel using
  7. additiona mixture of trichloromethane and methanol (97:3 by volume) as eluent
  8. customThe pure fractions were collected
  9. customthe eluent was evaporated
  10. filtrationThe salt was filtered off
  11. customdried

Sources & evidence

ORD record
ord-9297775d2c0c4abd865d040dfe4b3d3c
Source dataset
uspto-grants-1990_11
Patent number
US04968684

Reaction notes

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