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llms.txt · MCP 가이드개인정보처리방침 · 이용약관 · 지원v1.8.0
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tert-Butyl 4-nicotinoylpiperidine-1-carboxylate → tert-Butyl 4-((4-chloro-3-phenyl-2-(trifluoromethyl)quinolin-6-yl)(hydroxy)(pyridin-3-yl)methyl)piperidine-1-carboxylate

HRID 1478527
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HRID 1478527 반응식
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9](I)[CH:10]=2)[N:5]=[C:4]([C:13]([F:16])([F:15])[F:14])[C:3]=1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C([Mg]Cl)(C)C.[C:28]([CH:36]1[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][CH2:37]1)(=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[N:31][CH:30]=1>C1COCC1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:28]([OH:35])([C:29]3[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=3)[CH:36]3[CH2:37][CH2:38][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:40][CH2:41]3)[CH:10]=2)[N:5]=[C:4]([C:13]([F:16])([F:15])[F:14])[C:3]=1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
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참가 물질

5

반응물 3

HCID 19698705tert-Butyl 4-nicotinoylpiperidine-1-carboxylate2회HCID 867160644-Chloro-6-iodo-3-phenyl-2-(trifluoromethyl)quinoline2회HCID 178418918HCID 178418918, 화합물

생성물 1

HCID 118005527tert-Butyl 4-((4-chloro-3-phenyl-2-(trifluoromethyl)quinolin-6-yl)(hydroxy)(pyridin-3-yl)methyl)piperidine-1-carboxylate

시약·촉매·용매 1

HCID 8028
Tetrahydrofuran
용매

반응 조건

온도
50 °C

실험 절차

To a solution of 4-chloro-6-iodo-3-phenyl-2-(trifluoromethyl)quinoline (Intermediate 20: step b, containing about 13% molar of 4-chloro-3-phenyl-2-(trifluoromethyl)quinoline as impurity, 340 mg) in THF (4 mL) at −78° C. under N2 was added iPrMgCl (2.0 M in THF, 0.40 mL, 0.8 mmol). After stirring for 8 minutes, the cooling bath was removed, and stirring was continued for 20 minutes, then tert-butyl 4-nicotinoylpiperidine-1-carboxylate (225 mg, 0.770 mmol, Intermediate 21) was added in neat. After stirring at room temperature overnight, the mixture became clear brown and was heated at 50° C. for 1.5 hours. The mixture was quenched with saturated NH4Cl aqueous solution, and extracted with EtOAc. The extracts were dried over Na2SO4, filtered, and concentrated. The crude mixture was purified by flash column chromatography (silica gel, 20-100% EtOAc in heptanes) to provide the title compound. 1H NMR (400 MHz, CDCl3) δ 9.17-9.35 (m, 1H), 8.50-8.88 (m, 2H), 8.29 (d, J=7.58 Hz, 1H), 8.24 (d, J=8.59 Hz, 1H), 7.82-8.00 (m, 1H), 7.47-7.57 (m, 4H), 7.21-7.33 (m, 2H), 4.08-4.26 (m, 2H), 2.69-2.99 (m, 3H), 1.82-1.92 (m, 1H), 1.53-1.80 (m, 3H), 1.47 (s, 4.5H), 1.41 (s, 4.5H); MS m/e 598.3 [M+H]+.

후처리

  1. customthe cooling bath was removed
  2. stirringstirring
  3. waitwas continued for 20 minutes
  4. stirringAfter stirring at room temperature overnight
  5. customThe mixture was quenched with saturated NH4Cl aqueous solution
  6. extractionextracted with EtOAc
  7. dry with materialThe extracts were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude mixture was purified by flash column chromatography (silica gel, 20-100% EtOAc in heptanes)

출처 및 근거

ORD 기록
ord-997f79bbeb4d4884aa28f062fd3fec33
출처 데이터셋
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09403816B2

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