(3,3,3-Trifluoropropyl)hydrazine dihydrochloride → 3-((tert-butyldimethylsilyloxy)methyl)-2-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-5-yl)pyridine

HRID 1473911노트

반응식

HRID 1473911 반응식
[Si:1]([O:8][CH2:9][C:10]1[C:11]([C:16](=O)/[CH:17]=[CH:18]/[N:19](C)C)=[N:12][CH:13]=[CH:14][CH:15]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Cl.Cl.[F:25][C:26]([F:32])([F:31])[CH2:27][CH2:28][NH:29]N>CCO>[Si:1]([O:8][CH2:9][C:10]1[C:11]([C:16]2[N:29]([CH2:28][CH2:27][C:26]([F:32])([F:31])[F:25])[N:19]=[CH:18][CH:17]=2)=[N:12][CH:13]=[CH:14][CH:15]=1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3]

참가 물질

4

반응물 2

HCID 86690726(3,3,3-Trifluoropropyl)hydrazine dihydrochlorideHCID 86690729(E)-1-(3-((tert-butyldimethylsilyloxy)methyl)pyridin-2-yl)-3-(dimethylamino)prop-2-en-1-one

생성물 1

HCID 866907283-((tert-butyldimethylsilyloxy)methyl)-2-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-5-yl)pyridine수율 76%

시약·촉매·용매 1

HCID 702Ethanol용매

반응 조건

온도
80 °C

실험 절차

To (E)-1-(3-((tert-butyldimethylsilyloxy)methyl)pyridin-2-yl)-3-(dimethylamino)prop-2-en-1-one (crude above, 1.73 g, 5.41 mmol, 1 eq.) in EtOH (10 mL) was added (3,3,3-trifluoropropyl)hydrazine dihydrochloride (1.30 g, crude above, 6.49 mmol, 1.2 eq.) at rt. The mixture was heated at 80° C. for 1 h, concentrated, and diluted with EtOAc (50 mL) and NaHCO3(sat) solution (10 mL). The layers were separated and aqueous layer was extracted with EtOAc three times. The combined organic layers were dried over Na2SO4, concentrated, and purified on silica gel using a mixture of EtOAc and hexanes as eluent to give 3-((tert-butyldimethylsilyloxy)methyl)-2-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-5-yl)pyridine (1.58 g; 76% for 2 steps). 1H NMR (400 MHz, CDCl3) δ 8.53 (dd, J=4.7, 1.6 Hz, 1H), 7.96-7.88 (m, 1H), 7.51 (d, J=1.9 Hz, 1H), 7.29 (dd, J=7.9, 4.7 Hz, 1H), 6.34 (d, J=1.9 Hz, 1H), 4.62 (s, 2H), 4.45-4.33 (m, 2H), 2.82-2.61 (m, 2H), 0.85 (s, 8H), −0.00 (s, 5H). LRMS (M+H+) m/z 386.2.

후처리

  1. concentrationconcentrated
  2. additiondiluted with EtOAc (50 mL) and NaHCO3(sat) solution (10 mL)
  3. customThe layers were separated
  4. extractionaqueous layer was extracted with EtOAc three times
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. concentrationconcentrated
  7. custompurified on silica gel using
  8. additiona mixture of EtOAc and hexanes as eluent

출처 및 근거

ORD 기록
ord-3298fa0626f644fcb0bd5bf6a7960ca8
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018210B2

반응 노트

불러오는 중…