Cesium carbonate → (4-(7-chloro-1-(2,6-difluorophenyl)-4-methoxy-1H-pyrazolo[4,3-c]pyridin-3-yl)phenoxy)acetic acid

HRID 2206198

반응식

HRID 2206198 반응식
FC(F)(F)S(O[C:7]1[C:11]2[C:12]([O:17][CH3:18])=[N:13][CH:14]=[C:15]([Cl:16])[C:10]=2[N:9]([C:19]2[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=2[F:26])[N:8]=1)(=O)=O.CC1(C)C(C)(C)OB([C:37]2[CH:49]=[CH:48][C:40]([O:41][CH2:42][C:43]([O:45]CC)=[O:44])=[CH:39][CH:38]=2)O1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[Cl:16][C:15]1[C:10]2[N:9]([C:19]3[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=3[F:26])[N:8]=[C:7]([C:37]3[CH:49]=[CH:48][C:40]([O:41][CH2:42][C:43]([OH:45])=[O:44])=[CH:39][CH:38]=3)[C:11]=2[C:12]([O:17][CH3:18])=[N:13][CH:14]=1

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 3464653Ethyl 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)acetateHCID 1179882027-chloro-1-(2,6-difluorophenyl)-4-methoxy-1H-pyrazolo[4,3-c]pyridin-3-yl trifluoromethanesulfonate

생성물 1

HCID 117987738(4-(7-chloro-1-(2,6-difluorophenyl)-4-methoxy-1H-pyrazolo[4,3-c]pyridin-3-yl)phenoxy)acetic acid수율 66.1%

시약·촉매·용매 2

HCID 962Water용매2회HCID 6228Dimethylformamide용매

반응 조건

온도
90 °C

실험 절차

To a solution of 7-chloro-1-(2,6-difluorophenyl)-4-methoxy-1H-pyrazolo[4,3-c]pyridin-3-yl trifluoromethanesulfonate obtained in Step A of Example 152 (250 mg) in DMF (3 mL)/water (0.3 mL) were added ethyl (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)acetate (241 mg), (1,1′-bis(diphenylphosphino)ferrocene)dichloropalladium(II) (23 mg) and cesium carbonate (367 mg). The reaction mixture was stirred overnight at 90° C. The reaction mixture was diluted with water, and the aqueous layer was washed with ethyl acetate, and neutralized 1M hydrochloric acid at 0° C., and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (166 mg).

후처리

  1. washthe aqueous layer was washed with ethyl acetate, and neutralized 1M hydrochloric acid at 0° C.
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane)

출처 및 근거

ORD 기록
ord-2498a215641f42c89c65f86c4f27aa38
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09371320B2

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