Potassium Iodide → Methyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)-3-(r,s)-hydroxypropyl]-1-[2-(2,5-difluorophenylthio)ethyl]piperidine-4-carboxylate

HRID 395011노트

반응식

HRID 395011 반응식
Cl.Cl.[Cl:3][C:4]1[CH:5]=[N:6][C:7]2[C:12]([C:13]=1[CH2:14][CH2:15][CH2:16][C:17]1([C:23]([O:25][CH2:26]C)=[O:24])[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)=[CH:11][C:10]([O:28][CH3:29])=[CH:9][CH:8]=2.Br[CH2:31][CH2:32][S:33][C:34]1[CH:39]=[C:38]([F:40])[CH:37]=[CH:36][C:35]=1[F:41].[I-].[K+].C(=O)([O-])[O-:45].[K+].[K+]>C(#N)C.CN(C)C=O.O.C(OCC)C>[Cl:3][C:4]1[CH:5]=[N:6][C:7]2[C:12]([C:13]=1[CH:14]([OH:45])[CH2:15][CH2:16][C:17]1([C:23]([O:25][CH3:26])=[O:24])[CH2:22][CH2:21][N:20]([CH2:31][CH2:32][S:33][C:34]3[CH:39]=[C:38]([F:40])[CH:37]=[CH:36][C:35]=3[F:41])[CH2:19][CH2:18]1)=[CH:11][C:10]([O:28][CH3:29])=[CH:9][CH:8]=2

참가 물질

9

반응물 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 115216692-(2-bromoethylsulfanyl)-1,4-difluorobenzeneHCID 22468601Ethyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate dihydrochloride

생성물 1

HCID 22469786Methyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)-3-(r,s)-hydroxypropyl]-1-[2-(2,5-difluorophenylthio)ethyl]piperidine-4-carboxylate수율 28.3%

시약·촉매·용매 4

HCID 962Water용매HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매HCID 6342Acetonitrile용매

반응 조건

온도
85 °C

실험 절차

A mixture of 1.75 g of ethyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate dihydrochloride, 0.95 g of 2-(2-bromoethylthio)-1,4-difluorobenzene, 0.622 g of potassium iodide and 3.11 g of potassium carbonate in 30 cm3 of acetonitrile and 20 cm3 of dimethylformamide was heated with stirring for 18 hours at a temperature in the region of 85° C. After cooling to about 20° C., the reaction mixture was filtered through Celite and the filtrate was then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue obtained was taken up in water and diethyl ether. The organic phase was dried over magnesium sulfate, filtered and then concentrated to dryness as above. The residue obtained was purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 70-200μ; diameter 4 cm), eluting with a dichloromethane/methanol mixture (97.5/2.5 by volume). The fractions containing the product were combined and then concentrated to dryness according to the same conditions as above. 0.6 g of methyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)-3-(R,S)-hydroxypropyl]-1-[2-(2,5-difluorophenylthio)ethyl]piperidine-4-carboxylate was obtained.

후처리

  1. temperaturewas heated
  2. temperatureAfter cooling to about 20° C.
  3. filtrationthe reaction mixture was filtered through Celite
  4. concentrationthe filtrate was then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
  5. customThe residue obtained
  6. dry with materialThe organic phase was dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness as above
  9. customThe residue obtained
  10. customwas purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 70-200μ; diameter 4 cm)
  11. washeluting with a dichloromethane/methanol mixture (97.5/2.5 by volume)
  12. additionThe fractions containing the product
  13. concentrationconcentrated to dryness

출처 및 근거

ORD 기록
ord-e0d5f3f740de440c82b20595100bbd6e
출처 데이터셋
uspto-grants-2003_08
특허 번호
US06603005B2

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