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(R)-4-((R)-1-(6-(1-tert-butyl-1H-pyrazol-4-yl)-3-(difluoromethyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one → (R)-4-((R)-1-(6-(1-tert-butyl-1H-pyrazol-4-yl)-3-(difluoromethyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one

HRID 2209058
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HRID 2209058 반응식
[C:1]([N:5]1[CH:9]=[C:8]([C:10]2[N:15]=[C:14]([O:16][C@@H:17]([C@H:19]3[CH2:23][N:22]([C@@H](C4C=CC(OC)=CC=4)C)[C:21](=[O:34])[CH2:20]3)[CH3:18])[C:13]3[N:35]([CH:38]([F:40])[F:39])[CH:36]=[N:37][C:12]=3[CH:11]=2)[CH:7]=[N:6]1)([CH3:4])([CH3:3])[CH3:2]>C(O)(C(F)(F)F)=O>[C:1]([N:5]1[CH:9]=[C:8]([C:10]2[N:15]=[C:14]([O:16][C@@H:17]([C@H:19]3[CH2:23][NH:22][C:21](=[O:34])[CH2:20]3)[CH3:18])[C:13]3[N:35]([CH:38]([F:40])[F:39])[CH:36]=[N:37][C:12]=3[CH:11]=2)[CH:7]=[N:6]1)([CH3:2])([CH3:3])[CH3:4]
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참가 물질

3

반응물 1

HCID 117843539(R)-4-((R)-1-(6-(1-tert-butyl-1H-pyrazol-4-yl)-3-(difluoromethyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

생성물 1

HCID 117842962(R)-4-((R)-1-(6-(1-tert-butyl-1H-pyrazol-4-yl)-3-(difluoromethyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one

시약·촉매·용매 1

HCID 6422Trifluoroacetic acid용매

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온도
60 °C

실험 절차

(R)-4-((R)-1-(6-(1-tert-butyl-1H-pyrazol-4-yl)-3-(difluoromethyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 2.34 (max. 0.107 mmol) was dissolved in TFA (2 mL) and heated to 60° C. with stirring. After 15 h, the red solution was concentrated in vacuo and diluted with EtOAc (20 mL) and 1:1 saturated aqueous NaHCO3: brine (20 mL). The phases were separated and the aqueous phase was extracted with EtOAc (20 mL). The combined organic phase was dried over Na2SO4, filtered, and concentrated onto silica gel. Purification by silica gel chromatography (40% to 100% acetone in hexanes) provided (R)-4-((R)-1-(6-(1-tert-butyl-1H-pyrazol-4-yl)-3-(difluoromethyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one 3.03.

후처리

  1. concentrationthe red solution was concentrated in vacuo
  2. additiondiluted with EtOAc (20 mL) and 1:1 saturated aqueous NaHCO3
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with EtOAc (20 mL)
  5. dry with materialThe combined organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated onto silica gel
  8. customPurification by silica gel chromatography (40% to 100% acetone in hexanes)

출처 및 근거

ORD 기록
ord-d5d22c3e15f549efaf508e748b8f9986
출처 데이터셋
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09376441B2

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