Potassium Carbonate → (S)-ethyl-1-((2-(1-methylethylsulfonamido)-2,3-dihydro-1H-inden-5-yl)methyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate

HRID 42988

反応式

HRID 42988 の反応式
O[CH2:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[CH2:8][C@H:7]([NH:12][S:13]([CH:16]([CH3:18])[CH3:17])(=[O:15])=[O:14])[CH2:6]2.S(Cl)(Cl)=O.C(=O)([O-])[O-].[K+].[K+].[F:29][C:30]([F:42])([F:41])[C:31]1[C:35]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[CH:34][NH:33][N:32]=1>C(Cl)Cl.CN(C)C=O>[CH2:39]([O:38][C:36]([C:35]1[C:31]([C:30]([F:41])([F:42])[F:29])=[N:32][N:33]([CH2:2][C:3]2[CH:4]=[C:5]3[C:9](=[CH:10][CH:11]=2)[CH2:8][C@H:7]([NH:12][S:13]([CH:16]([CH3:18])[CH3:17])(=[O:15])=[O:14])[CH2:6]3)[CH:34]=1)=[O:37])[CH3:40]

参加物

7

反応物 4

HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 67088215(S)-N-(5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamideHCID 178469923HCID 178469923、化合物

生成物 1

HCID 67088144(S)-ethyl-1-((2-(1-methylethylsulfonamido)-2,3-dihydro-1H-inden-5-yl)methyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate収率 55.1%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

(S)—N-(5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide (2.57 mmol, 692 mg) was dissolved in DCM (10 mL), thionyl chloride (5.14 mmol, 0.373 mL, 611 mg) added and the solution stirred at room temperature. After 45 min the mixture was concentrated then azeotroped with dichloromethane (4×10 mL) to give a yellow oil. To this oil was added dimethylformamide (10 mL) and potassium carbonate (7.71 mmol, 1.07 g) followed by ethyl 3-(trifluoromethyl)-1H-pyrazole-4-carboxylate (2.57 mmol, 0.54 g). The mixture was heated to 70° C. with stirring for 1 h. The reaction was concentrated to remove DMF before partitioning between EtOAc/water. The phases were mixed and separated and the aqueous phase further washed with EtOAc (×2). Combined organics were dried and concentrated to give a light yellow oil which was purified on silica eluting with 30% EtOAc/heptane. Desired fractions were collected and concentrated to give (S)-ethyl-1-((2-(1-methylethylsulfonamido)-2,3-dihydro-1H-inden-5-yl)methyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate as a colourless solid (0.65 g, 55.1%). 1H NMR (400 MHz, CDCl3) δ 1.33 (t, 3H) 1.39 (d, 6H) 2.9 (m, 2H) 3.17 (sept, 1H) 3.30 (m, 2H) 4.30 (m, 4H) 5.29 (s, 2H) 7.12 (m, 2H) 7.24 (d, 1H) 7.89 (s, 1H)

後処理

  1. concentrationAfter 45 min the mixture was concentrated
  2. customthen azeotroped with dichloromethane (4×10 mL)
  3. customto give a yellow oil
  4. temperatureThe mixture was heated to 70° C.
  5. stirringwith stirring for 1 h
  6. concentrationThe reaction was concentrated
  7. customto remove DMF
  8. custombefore partitioning between EtOAc/water
  9. additionThe phases were mixed
  10. customseparated
  11. washthe aqueous phase further washed with EtOAc (×2)
  12. customCombined organics were dried
  13. concentrationconcentrated
  14. customto give a light yellow oil which
  15. customwas purified on silica eluting with 30% EtOAc/heptane
  16. customDesired fractions were collected
  17. concentrationconcentrated

出典と根拠

ORDレコード
ord-829a457dda4a44d1bc640a618bb6cbcf
出典データセット
uspto-grants-2013_09
特許番号
US08536214B2

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