Triethylamine → 3-chloro-N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-4-(methylsulfonyl)thiophene-2-carboxamide

HRID 548007

反応式

HRID 548007 の反応式
Cl.[CH3:2][C:3]1[C:7]([CH2:8][N:9]2[CH:13]=[C:12]([NH2:14])[CH:11]=[N:10]2)=[C:6]([CH3:15])[O:5][N:4]=1.C(N(CC)CC)C.[Cl:23][C:24]1[C:28]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:27][S:26][C:25]=1[C:33](Cl)=[O:34]>C(Cl)Cl.CC#N>[Cl:23][C:24]1[C:28]([S:29]([CH3:32])(=[O:30])=[O:31])=[CH:27][S:26][C:25]=1[C:33]([NH:14][C:12]1[CH:11]=[N:10][N:9]([CH2:8][C:7]2[C:3]([CH3:2])=[N:4][O:5][C:6]=2[CH3:15])[CH:13]=1)=[O:34]

参加物

6

反応物 3

HCID 8471TriethylamineHCID 27357753-Chloro-4-(Methylsulfonyl)Thiophene-2-Carbonyl ChlorideHCID 574222641-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-amine hydrochloride

生成物 1

HCID 43413323-chloro-N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-4-(methylsulfonyl)thiophene-2-carboxamide収率 45.2%

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

To a stirring mixture of ((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-amine hydrochloride (Example 4-1a) (500 mg, 2 mmol) in DCM (20 mL), cooled to 0° C. via an ice water bath, was added triethylamine (600 mg, 6 mmol). The mixture was stirred until all solids were in solution (˜10 minutes). 3-Chloro-4-(methylsulfonyl)thiophene-2-carbonyl chloride (543 mg, 2.1 mmol), in 2 mL CH3CN, was added via syringe to the free amine at 0° C. The ice bath was removed and the mixture was stirred for 2 hours. The reaction was diluted with dichloromethane (100 mL) and the organic phase was washed with H2O (200 mL). The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The solid was triturated with ethyl acetate/hexanes (1/5) to afford 3-chloro-N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-4 (methylsulfonyl)thiophene-2-carboxamide (375 mg, 45%) as a white solid. 1H NMR (CDCl3, 400 MHz):2.20 (s, 3H), 2.43 (s, 4H), 3.22 (s, 3H), 5.05 (s, 2H), 7.57 (s, 1H), 7.94 (s, 1H), 8.41 (s, 1H), 8.59 (bs, 1H). LC/MS; [M+H] 415.5. Melting point: 202-204° C.

後処理

  1. customwere in solution (˜10 minutes)
  2. customThe ice bath was removed
  3. stirringthe mixture was stirred for 2 hours
  4. additionThe reaction was diluted with dichloromethane (100 mL)
  5. washthe organic phase was washed with H2O (200 mL)
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe solid was triturated with ethyl acetate/hexanes (1/5)

出典と根拠

ORDレコード
ord-9fa91a87d88045aab0b41576317b7e2e
出典データセット
uspto-grants-2011_05
特許番号
US07939671B2

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