Water → 2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid [4-chloro-2-methyl-6-(thietan-3-ylcarbamoyl)-phenyl]-amide

HRID 660129Notes

Reaction equation

HRID 660129 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH3:29])[C:5]2[N:10]=[C:9]([C:11]3[N:15]([C:16]4[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][N:17]=4)[N:14]=[C:13]([C:23]([F:26])([F:25])[F:24])[CH:12]=3)[O:8][C:7](=[O:27])[C:6]=2[CH:28]=1.C(N(CC)CC)C.Br.[S:38]1[CH2:41][CH:40]([NH2:42])[CH2:39]1.O>O1CCCC1>[Cl:1][C:2]1[CH:28]=[C:6]([C:7](=[O:27])[NH:42][CH:40]2[CH2:41][S:38][CH2:39]2)[C:5]([NH:10][C:9]([C:11]2[N:15]([C:16]3[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][N:17]=3)[N:14]=[C:13]([C:23]([F:24])([F:25])[F:26])[CH:12]=2)=[O:8])=[C:4]([CH3:29])[CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 231503516-chloro-2-[2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazol-3-yl]-8-methylbenzo[d][1,3]oxazin-4-oneHCID 53346555Thietan-3-amine hydrobromide2×

Product 1

HCID 593935962-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid [4-chloro-2-methyl-6-(thietan-3-ylcarbamoyl)-phenyl]-amideYield 41%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazin-4-one (500 mg, 1.13 mmol) [prepared according to WO 02/48115, example 2D] in tetrahydrofuran (10 ml) is added triethylamine (0.4 ml, 2.87 mmol) and 3-thietanamine hydrobromide salt [the product of step 2] (250 mg, 1.47 mmol), and the mixture is heated to reflux overnight. The cooled reaction mixture is poured into water, extracted with ethyl acetate, the combined organic layers washed with water and brine, dried (Na2SO4), filtered, and concentrated. The crude product is purified by flash chromatography (ethyl acetate/hexane 1:2) to afford 250 mg (41%) of the title compound as a white solid.

Workup

  1. temperaturethe mixture is heated
  2. temperatureto reflux overnight
  3. customThe cooled reaction mixture
  4. extractionextracted with ethyl acetate
  5. washthe combined organic layers washed with water and brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product is purified by flash chromatography (ethyl acetate/hexane 1:2)

Sources & evidence

ORD record
ord-86eb829963ad4b1396532726bd6e2ca5
Source dataset
uspto-grants-2011_12
Patent number
US08084474B2

Reaction notes

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