Diisopropylethylamine → 5-amino-N-(2-((N-ethyl-2,6-difluorobenzamido)methyl)-3,3,3-trifluoro-2-hydroxypropyl)-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide

HRID 886721Notes

Reaction equation

HRID 886721 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:14]([NH:16][CH2:17][C:18]([CH2:24][NH:25][CH2:26][CH3:27])([OH:23])[C:19]([F:22])([F:21])[F:20])=[O:15].C(N(C(C)C)CC)(C)C.[F:37][C:38]1[CH:46]=[CH:45][CH:44]=[C:43]([F:47])[C:39]=1[C:40](Cl)=[O:41]>ClCCl>[NH2:1][C:2]1[N:6]([C:7]2[CH:8]=[CH:9][C:10]([F:13])=[CH:11][CH:12]=2)[N:5]=[CH:4][C:3]=1[C:14]([NH:16][CH2:17][C:18]([CH2:24][N:25]([C:40]([C:39]1[C:38]([F:37])=[CH:46][CH:45]=[CH:44][C:43]=1[F:47])=[O:41])[CH2:26][CH3:27])([OH:23])[C:19]([F:22])([F:21])[F:20])=[O:15]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 874382,6-Difluorobenzoyl chlorideHCID 59187223HCID 59187223, compound

Product 1

HCID 248097115-amino-N-(2-((N-ethyl-2,6-difluorobenzamido)methyl)-3,3,3-trifluoro-2-hydroxypropyl)-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamideYield 94.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 5-amino-N-{2-[(ethylamino)methyl]-3,3,3-trifluoro-2-hydroxypropyl}-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide (0.277 g, 0.712 mmol) in dry dichloromethane (ca. 11 ml), diisopropylethylamine (0.245 ml, 1.42 mmol) was added and then cooled in a freezer to −10 to −15° C. before a similarly cooled solution of 2,6-difluorobenzoyl chloride (0.123 g, 0.712 mmol) in dichloromethane (2 ml) was added with stirring. The mixture was stirred for 1 minute and then allowed to stand in the fridge for approx. 2 hours and then allowed to warm to room temperature. The next day the mixture was evaporated under reduced pressure and purified on a column of silica. Elution with 2% ethanol in chloroform gave, upon evaporation under reduced pressure, a clear glass (0.421 g) which, upon scraping, gave the title compound (0.356 g) as a white solid.

Workup

  1. additionwas added
  2. stirringThe mixture was stirred for 1 minute
  3. customThe next day the mixture was evaporated under reduced pressure
  4. custompurified on a column of silica
  5. washElution with 2% ethanol in chloroform
  6. customgave, upon evaporation under reduced pressure

Sources & evidence

ORD record
ord-f3381deee4a24b4a971f0bf8129310ed
Source dataset
uspto-grants-2012_08
Patent number
US08247377B2

Reaction notes

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