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Triphenylphosphine → 2-((4S,5S)-1-(4-((1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl)oxy)phenyl)-4-ethyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-yl)acetonitrile

HRID 2278687
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HRID 2278687 반응식
[Cl:1][C:2]1[C:3]([N:10]2[CH2:15][CH2:14][CH:13]([O:16][C:17]3[CH:22]=[CH:21][C:20]([N:23]4[CH:27]([CH2:28][C:29]#[N:30])[CH:26]([CH2:31][CH3:32])[C:25]([C:33]([F:36])([F:35])[F:34])=[N:24]4)=[CH:19][CH:18]=3)[CH:12]([CH3:37])[CH2:11]2)=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.C(C1C(CC#N)N(C2C=CC(O)=CC=2)N=C1C(F)(F)F)C.ClC1C(N2CC[C@H](O)[C@H](C)C2)=CC(OC)=NC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(/C(OC(C)(C)C)=O)=N\C(OC(C)(C)C)=O.C([O-])(O)=O.[Na+]>C1COCC1>[Cl:1][C:2]1[C:3]([N:10]2[CH2:15][CH2:14][CH:13]([O:16][C:17]3[CH:22]=[CH:21][C:20]([N:23]4[C@@H:27]([CH2:28][C:29]#[N:30])[C@H:26]([CH2:31][CH3:32])[C:25]([C:33]([F:36])([F:34])[F:35])=[N:24]4)=[CH:19][CH:18]=3)[CH:12]([CH3:37])[CH2:11]2)=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

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반응물 6

HCID 11776TriphenylphosphineHCID 516892Sodium BicarbonateHCID 6034084Di-tert-butyl diazene-1,2-dicarboxylateHCID 86719424(3R,4S)-1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-olHCID 867194262-(1-(4-((1-(5-Chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl)oxy)phenyl)-4-ethyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-yl)acetonitrile
HCID 86719427
2-(4-ethyl-1-(4-hydroxyphenyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-yl)acetonitrile

생성물 1

HCID 867194252-((4S,5S)-1-(4-((1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl)oxy)phenyl)-4-ethyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-yl)acetonitrile수율 26%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

2-(1-(4-((1-(5-Chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl)oxy)phenyl)-4-ethyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-yl)acetonitrile: To a solution of 2-(4-ethyl-1-(4-hydroxyphenyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-yl)acetonitrile (174 mg, 0.58 mmol) and (3R,4S)-1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-ol (150 mg, 0.58 mmol) in THF (195 μl) was added triphenylphosphine (215 mg, 0.82 mmol). The reaction vessel was then lowered into a sonication bath and sonicated for several minutes (to allow for mixing) giving a clear and highly viscous solution. While sonicating, (E)-di-tert-butyl diazene-1,2-dicarboxylate (161 mg, 0.70 mmol) was added dropwise to the reaction mixture, and the reaction mixture was sonicated for 120 min. LCMS showed the desired mass of product. Then, sat. aq. NaHCO3 (10 mL) was added slowly to the reaction mixture. The mixture was then extracted with EtOAc (2×10 mL), and the combined organic extracts were washed with water (20 mL) and brine (20 mL), and dried (Na2SO4), filtered, and concentrated. Purification by chromatography gave 2-((4S,5S)-1-(4-((1-(5-chloro-2-methoxypyridin-4-yl)-3-methylpiperidin-4-yl)oxy)phenyl)-4-ethyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-yl)acetonitrile (80 mg, 0.15 mmol, 26% yield) an oil. LC-MS Anal. Calc'd for C26H29ClF3N5O2 535.20. found [M+H] 536.0.

후처리

  1. customThe reaction vessel was then lowered into a sonication bath
  2. customsonicated for several minutes
  3. addition(to allow for mixing)
  4. customgiving a clear and highly viscous solution
  5. customWhile sonicating
  6. customthe reaction mixture was sonicated for 120 min
  7. extractionThe mixture was then extracted with EtOAc (2×10 mL)
  8. washthe combined organic extracts were washed with water (20 mL) and brine (20 mL)
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification by chromatography

출처 및 근거

ORD 기록
ord-fb6d7b18a39748de9c1a49ab2630ed5f
출처 데이터셋
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09133163B2

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