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

HRID 660124Notes

Reaction equation

HRID 660124 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.[NH2:30][C:31]1([CH3:35])[CH2:34][S:33][CH2:32]1.O>O1CCCC1>[Cl:1][C:2]1[CH:28]=[C:6]([C:7](=[O:27])[NH:30][C:31]2([CH3:35])[CH2:34][S:33][CH2:32]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:26])([F:25])[F:24])[CH:12]=2)=[O:8])=[C:4]([CH3:29])[CH:3]=1

Participants

5

Reactant 3

HCID 962WaterHCID 231503516-chloro-2-[2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazol-3-yl]-8-methylbenzo[d][1,3]oxazin-4-oneHCID 552816773-Methylthietan-3-amine2×

Product 1

HCID 593935852-(3-Chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid [4-chloro-2-methyl-6-(3-methyl-thietan-3-ylcarbamoyl)-phenyl]-amideYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

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 (1.13 g, 2.56 mmol) (prepared according to WO 02/48115, example 2D) in tetrahydrofuran (15 ml) is added 3-amino-3-methyl-thietane (the product of step 3) (0.66 g, 6.40 mmol), and the mixture is heated for 48 hours at 50° C., then to reflux for 12 hours. 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 560 mg (40%) of the title compound as a white solid, m.p. 238-241° C.

Workup

  1. temperatureto reflux for 12 hours
  2. customThe cooled reaction mixture
  3. extractionextracted with ethyl acetate
  4. washthe combined organic layers washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product is purified by flash chromatography (ethyl acetate/hexane 1:2)

Sources & evidence

ORD record
ord-8c1ca71d6ef74173a4af3f5c8b120ab3
Source dataset
uspto-grants-2011_12
Patent number
US08084474B2

Reaction notes

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