Isopropanol → Methyl 1-(3-((1-(quinolin-2-YL)piperidin-4-YL)oxy)pyrazin-2-YL)piperidine-4-carboxylate

HRID 454927노트

반응식

HRID 454927 반응식
Cl[C:2]1[C:3]([O:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:24]=[CH:23][C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[N:16]=3)[CH2:11][CH2:10]2)=[N:4][CH:5]=[CH:6][N:7]=1.[NH:25]1[CH2:30][CH2:29][CH:28]([C:31]([O:33][CH3:34])=[O:32])[CH2:27][CH2:26]1.C([O-])([O-])=O.[K+].[K+].CC(O)C>O>[N:16]1[C:17]2[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:23]=[CH:24][C:15]=1[N:12]1[CH2:13][CH2:14][CH:9]([O:8][C:3]2[C:2]([N:25]3[CH2:30][CH2:29][CH:28]([C:31]([O:33][CH3:34])=[O:32])[CH2:27][CH2:26]3)=[N:7][CH:6]=[CH:5][N:4]=2)[CH2:10][CH2:11]1

참가 물질

6

반응물 4

HCID 3776IsopropanolHCID 11430Potassium CarbonateHCID 424914Methyl isonipecotateHCID 585476872-(4-((3-Chloropyrazin-2-yl)oxy)piperidin-1-yl)quinoline

생성물 1

HCID 58547953Methyl 1-(3-((1-(quinolin-2-YL)piperidin-4-YL)oxy)pyrazin-2-YL)piperidine-4-carboxylate수율 27%

시약·촉매·용매 1

HCID 962Water용매

반응 조건

온도
160 °C

실험 절차

To a mixture of 2-[4-(3-chloro-pyrazin-2-yloxy)-piperidin-1-yl]-quinoline (see PREPARATION P2.1; 0.34 g, 1.0 mmol) and methyl piperidine-4-carboxylate (0.14 g, 1.0 mmol) and K2CO3 (0.27 g, 2.0 mmol) was added i-PrOH (2 mL) and water (0.5 ml). The solution was heated to 160° C. under microwave for 5 hours. Then the mixture was concentrated and extracted with EtOAc (2×20 mL). The combined organic extracts were washed with water (10 mL) and brine (10 mL), dried over Na2SO4, and filtered. The filtrate was evaporated in vacuo and the residue was purified by flash column chromatography on silica gel (20% to 60% EtOAc in petroleum ether) to give the title product (0.12 g, 0.27 mmol, 27% yield) as white solid. ESI-MS (M+1): 448 calc. for C25H29N5O3 447.

후처리

  1. concentrationThen the mixture was concentrated
  2. extractionextracted with EtOAc (2×20 mL)
  3. washThe combined organic extracts were washed with water (10 mL) and brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customThe filtrate was evaporated in vacuo
  7. customthe residue was purified by flash column chromatography on silica gel (20% to 60% EtOAc in petroleum ether)

출처 및 근거

ORD 기록
ord-9fee865f9be645d595bdf4f457cb66af
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08497265B2

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