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 43001노트

반응식

HRID 43001 반응식
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]

참가 물질

6

반응물 4

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

생성물 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-sulfonamide수율 20%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

(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

후처리

  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

출처 및 근거

ORD 기록
ord-a0d726bb004c40319d60c3962ede42b4
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08536214B2

반응 노트

불러오는 중…