Triethylamine → (1,1-Dimethylethyl) [[4-[[2-[2-(aminocarbonyl)-4-[5,5-bis(4-fluorophenyl)pentyl]-1-piperazinyl]acetyl]amino]-3,5-dichlorophenyl]methyl]carbamate

HRID 1073183Notes

Reaction equation

HRID 1073183 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH2:9][CH2:10][CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][NH:16][CH:15]([C:19]([NH2:21])=[O:20])[CH2:14]2)=[CH:4][CH:3]=1.[Cl:29][C:30]1[CH:31]=[C:32]([CH2:42][NH:43][C:44](=[O:50])[O:45][C:46]([CH3:49])([CH3:48])[CH3:47])[CH:33]=[C:34]([Cl:41])[C:35]=1[NH:36][C:37](=[O:40])[CH2:38]Cl.C(N(CC)CC)C>CN(C)C=O>[NH2:21][C:19]([CH:15]1[CH2:14][N:13]([CH2:12][CH2:11][CH2:10][CH2:9][CH:8]([C:22]2[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=2)[C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[CH2:18][CH2:17][N:16]1[CH2:38][C:37]([NH:36][C:35]1[C:34]([Cl:41])=[CH:33][C:32]([CH2:42][NH:43][C:44](=[O:50])[O:45][C:46]([CH3:48])([CH3:47])[CH3:49])=[CH:31][C:30]=1[Cl:29])=[O:40])=[O:20]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 147225494-[5,5-Bis(4-fluorophenyl)pentyl]-2-piperazinecarboxamideHCID 14722566(1,1-Dimethylethyl) [[3,5-dichloro-4-[(2-chloroacetyl)amino]phenyl)methyl)carbamate

Product 1

HCID 14722567(1,1-Dimethylethyl) [[4-[[2-[2-(aminocarbonyl)-4-[5,5-bis(4-fluorophenyl)pentyl]-1-piperazinyl]acetyl]amino]-3,5-dichlorophenyl]methyl]carbamateYield 80.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 7 parts of 4-[5,5-bis(4-fluorophenyl)pentyl]-2-piperazinecarboxamide, 6.6 parts of (1,1-dimethylethyl) [[3,5-dichloro-4-[(2-chloroacetyl)amino]phenyl)methyl)carbamate, 2.8 parts of N,N-diethylethanamine and 94 parts of N,N-dimethylformamide was stirred over weekend 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, saturated with ammonia, (96:4 by volume) as eluent. The desired fractions were collected and the eluent was evaporated, yielding 8.7 parts (80.7%) of (1,1-dimethylethyl) [[4-[[2-[2-(aminocarbonyl)-4-[5,5-bis(4-fluorophenyl)pentyl]-1-piperazinyl]acetyl]amino]-3,5-dichlorophenyl]methyl]carbamate as a residue (int. 102).

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
  9. customThe desired fractions were collected
  10. customthe eluent was evaporated

Sources & evidence

ORD record
ord-1c15dfe291d34cfc9fa08e30a30cd558
Source dataset
uspto-grants-1990_11
Patent number
US04968684

Reaction notes

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