Diisopropylethylamine → (2,6-difluorophenyl)-N-{5-[1-methyl-3-(trifluoromethyl)pyrazol-5-yl](1,3-thiazol-2-yl)}carboxamide

HRID 1524244Notes

Reaction equation

HRID 1524244 reaction equation
[CH3:1][N:2]1[C:6]([C:7]2[S:11][C:10]([NH2:12])=[N:9][CH:8]=2)=[CH:5][C:4]([C:13]([F:16])([F:15])[F:14])=[N:3]1.[F:17][C:18]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[C:19]=1[C:20](Cl)=[O:21].CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C1C=CN=CC=1)C>[F:17][C:18]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[C:19]=1[C:20]([NH:12][C:10]1[S:11][C:7]([C:6]2[N:2]([CH3:1])[N:3]=[C:4]([C:13]([F:16])([F:14])[F:15])[CH:5]=2)=[CH:8][N:9]=1)=[O:21]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 874382,6-Difluorobenzoyl chlorideHCID 866626835-[1-Methyl-3-(trifluoromethyl)pyrazol-5-yl]-1,3-thiazole-2-ylamine

Product 1

HCID 56848090(2,6-difluorophenyl)-N-{5-[1-methyl-3-(trifluoromethyl)pyrazol-5-yl](1,3-thiazol-2-yl)}carboxamideYield 75.9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of 5-[1-methyl-3-(trifluoromethyl)pyrazol-5-yl]-1,3-thiazole-2-ylamine (63, 4.6 mg, 0.019 mmol) in 0.5 ml DCM were added 2,6-difluorobenzoyl chloride (5 μl, 2 eq), DIEA (17 μl, 3 eq) and DMAP (2 mg). After stirred at r.t for overnight, the reaction mixture was worked up with DCM/aq. NaCO3, the DCM phase was concentrated to dryness. The solid residue was dissolved in 1 ml THF/MeOH/H2O (5:4:1). 0.1 ml of 1N NaOH were added and mixture was stirred at r.t for 1 h before worked up DCM//aq. NaCO3. DCM phase was concentrated and subjected to silica gel flash column to give 5.6 mg of (2,6-difluorophenyl)-N-{5-[1-methyl-3-(trifluoromethyl)pyrazol-5-yl] (1,3-thiazol-2-yl)}carboxamide (64) as white solid (yield: 75.9%; purity>95%). LC-MS: calcd. for C15H9F5N4OS: 389 (M+1).

Workup

  1. concentrationNaCO3, the DCM phase was concentrated to dryness
  2. dissolutionThe solid residue was dissolved in 1 ml THF/MeOH/H2O (5:4:1)
  3. addition0.1 ml of 1N NaOH were added
  4. stirringmixture was stirred at r.t for 1 h
  5. concentrationDCM phase was concentrated

Sources & evidence

ORD record
ord-3f52377936e042c7a4f9579b6e520c0d
Source dataset
uspto-grants-2015_07
Patent number
US09079891B2

Reaction notes

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