Potassium Carbonate → (R)-N-(5-((4-(2-hydroxypropan-2-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide

HRID 43001ノート

反応式

HRID 43001 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.[F:23][C:24]([F:35])([F:34])[C:25]1[C:29]([C:30]([OH:33])([CH3:32])[CH3:31])=[CH:28][NH:27][N:26]=1.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl>[OH:33][C:30]([C:29]1[C:25]([C:24]([F:35])([F:34])[F:23])=[N:26][N:27]([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:28]=1)([CH3:32])[CH3:31]

参加物

6

反応物 4

HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 67025426(R)-N-(5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamideHCID 178458810HCID 178458810、化合物

生成物 1

HCID 44555608(R)-N-(5-((4-(2-hydroxypropan-2-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide収率 20%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

(R)—N-(5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide (30 mg, 0.11 mmol) was dissolved in DCM (5 mL) and thionyl chloride (66 mg, 0.57 mmol) was added. The reaction mixture was stirred at room temperature for 1 h before being concentrated to dryness. The whole was dissolved in DMF (2 mL) and 2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)propan-2-ol (21.6 mg, 0.11 mmol) was added followed by potassium carbonate (30.8 mg, 0.22 mmol). The reaction mixture was stirred at room temperature overnight before being quenched with water (2 mL) and the organics extracted with EtOAc (3×5 mL). The combined organics were washed with brine, dried (MgSO4) and concentrated under reduced pressure. Purification by preparative basic HPLC gave (R)—N-(5-((4-(2-hydroxypropan-2-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide (9.6 mg, 0.022 mmol, 19.4%). MS (ESI): m/z [M+H]+ 446.5

後処理

  1. concentrationbefore being concentrated to dryness
  2. dissolutionThe whole was dissolved in DMF (2 mL)
  3. stirringThe reaction mixture was stirred at room temperature overnight
  4. custombefore being quenched with water (2 mL)
  5. extractionthe organics extracted with EtOAc (3×5 mL)
  6. washThe combined organics were washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated under reduced pressure
  9. customPurification by preparative basic HPLC

出典と根拠

ORDレコード
ord-a0d726bb004c40319d60c3962ede42b4
出典データセット
uspto-grants-2013_09
特許番号
US08536214B2

反応ノート

読み込み中…