Triethylamine → N-(4-acetyl-2,6-dichlorophenyl)-4-[4-[bis(4-fluorophenyl)amino]butyl]-3-[(methylamino)carbonyl]-1-piperazineacetamide

HRID 1073188Notes

Reaction equation

HRID 1073188 reaction equation
Cl[CH2:2][CH2:3][CH2:4][CH2:5][N: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:44])[CH2:33][N:34]2[CH2:39][CH2:38][NH:37][CH:36]([C:40]([NH:42][CH3:43])=[O:41])[CH2:35]2)=[C:26]([Cl:45])[CH:25]=1)(=[O:23])[CH3:22].C(N(CC)CC)C>COCCO>[C:21]([C:24]1[CH:29]=[C:28]([Cl:30])[C:27]([NH:31][C:32](=[O:44])[CH2:33][N:34]2[CH2:39][CH2:38][N:37]([CH2:2][CH2:3][CH2:4][CH2:5][N: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]([NH:42][CH3:43])=[O:41])[CH2:35]2)=[C:26]([Cl:45])[CH:25]=1)(=[O:23])[CH3:22]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 14722551N-(4-chlorobutyl)-4-fluoro-N-(4-fluorophenyl)benzenamineHCID 14722753N-(4-acetyl-2,6-dichlorophenyl)-3-[(methylamino)carbonyl]-1-piperazineacetamide

Product 1

HCID 14722700N-(4-acetyl-2,6-dichlorophenyl)-4-[4-[bis(4-fluorophenyl)amino]butyl]-3-[(methylamino)carbonyl]-1-piperazineacetamideYield 19%

Reagents, catalysts & solvents 1

HCID 80192-MethoxyethanolSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 2.07 parts of N-(4-chlorobutyl)-4-fluoro-N-(4-fluorophenyl)benzenamine, 2.5 parts of N-(4-acetyl-2,6-dichlorophenyl)-3-[(methylamino)carbonyl]-1-piperazineacetamide, 1.3 parts of N,N-diethylethanamine and 97 parts of 2-methoxyethanol was stirred for 3 days at 70° C. The reaction mixture was evaporated and the residue was taken up in water. The product was extracted twice with dichloromethane. The combined extracts were washed with water, dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (98:2 by volume) as eluent. The desired fraction was collected and the eluent was evaporated. The residue was crystallized from acetonitrlle. The product was filtered off and dried, yielding a first fraction of 0.74 parts (19.0%) of N-(4-acetyl-2.6-dichlorophenyl)-4-[4-[bis(4-fluorophenyl)amino]butyl]-3-[(methylamino)carbonyl]-1-piperazineacetamide mp. 87.1° C. The second fraction was collected and the eluent was evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding a second fraction of 0.78 parts (20.1%) of N-(4-acetyl-2,6-dichlorophenyl)-4-[4-[bis(4-fluorophenyl)amino]butyl]3-[(methylamino)carbonyl]-1-piperazineacetamide; mp. 85.0° C. Total yield: 1.52 parts (39.1%) of N-(4-acetyl-2,6-dichlorophenyl)-4-[4-[bis(4-fluorophenyl)amino]butyl]-3-[(methylamino)carbonyl]-1piperazineacetamide (compound 97).

Workup

  1. customThe reaction mixture was evaporated
  2. extractionThe product was extracted twice with dichloromethane
  3. washThe combined extracts were washed with water
  4. customdried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by column chromatography over silica gel using
  8. additiona mixture of trichloromethane and methanol (98:2 by volume) as eluent
  9. customThe desired fraction was collected
  10. customthe eluent was evaporated
  11. customThe residue was crystallized from acetonitrlle
  12. filtrationThe product was filtered off
  13. customdried

Sources & evidence

ORD record
ord-b53c224b3c1048bfbdd19e0e7599d7c7
Source dataset
uspto-grants-1990_11
Patent number
US04968684

Reaction notes

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