Acetic Acid → N-(1-Benzyl-4,4-diethoxy-piperidin-3-yl)-6-[2-ethyl-5-fluoro-4-(2-trimethylsilanyl-ethoxymethoxy)-phenyl]-1-(tetrahydro-pyran-2-yl)-1H-indazole-3-carboxamidine

HRID 2038712

반응식

HRID 2038712 반응식
CO[C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:19]=[C:18]([F:20])[C:17]([O:21][CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])=[CH:16][C:15]=3[CH2:30][CH3:31])=[CH:11][CH:12]=2)[N:7]([CH:32]2[CH2:37][CH2:36][CH2:35][CH2:34][O:33]2)[N:6]=1)=[NH:4].[CH2:38]([N:45]1[CH2:50][CH2:49][C:48]([O:54][CH2:55][CH3:56])([O:51][CH2:52][CH3:53])[CH:47]([NH2:57])[CH2:46]1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.C(O)(=O)C>C(O)C>[CH2:38]([N:45]1[CH2:50][CH2:49][C:48]([O:54][CH2:55][CH3:56])([O:51][CH2:52][CH3:53])[CH:47]([NH:57][C:3]([C:5]2[C:13]3[C:8](=[CH:9][C:10]([C:14]4[CH:19]=[C:18]([F:20])[C:17]([O:21][CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:27])[CH3:28])=[CH:16][C:15]=4[CH2:30][CH3:31])=[CH:11][CH:12]=3)[N:7]([CH:32]3[CH2:37][CH2:36][CH2:35][CH2:34][O:33]3)[N:6]=2)=[NH:4])[CH2:46]1)[C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1

참가 물질

5

반응물 3

HCID 176Acetic AcidHCID 217299351-Benzyl-4,4-diethoxypiperidin-3-amineHCID 866762716-[2-Ethyl-5-fluoro-4-(2-trimethylsilanyl-ethoxymethoxy)-phenyl]-1-(tetrahydro-pyran-2-yl)-1H-indazole-3-carboximidic acid methyl ester

생성물 1

HCID 178467533N-(1-Benzyl-4,4-diethoxy-piperidin-3-yl)-6-[2-ethyl-5-fluoro-4-(2-trimethylsilanyl-ethoxymethoxy)-phenyl]-1-(tetrahydro-pyran-2-yl)-1H-indazole-3-carboxamidine수율 45%

시약·촉매·용매 1

HCID 702Ethanol용매2회

반응 조건

온도
50 °C

실험 절차

To a solution of 6-[2-ethyl-5-fluoro-4-(2-trimethylsilanyl-ethoxymethoxy)-phenyl]-1-(tetrahydro-pyran-2-yl)-1H-indazole-3-carboximidic acid methyl ester (Preparation 7, 17.15 g, 32.49 mmol) in ethanol (100 mL) was added a solution of 1-benzyl-4,4-diethoxy-piperidin-3-ylamine (Tetrahedron, 1995, 51, 13447-13454; 9.51 g, 34.2 mmol) in ethanol (70 mL). Acetic acid (3.56 mL, 62.1 mmol) was added and the reaction mixture was heated at 50° C. for 18 hours. The reaction mixture was concentrated in vacuo and the residue was partitioned between EtOAc (400 mL) and saturated sodium hydrogen carbonate aqueous solution (300 mL). The organic layer was washed with further saturated sodium hydrogen carbonate aqueous solution (300 mL). The combined aqueous layers were re-extracted with EtOAc (400 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo. The crude product was purified by column chromatography on silica gel eluting with DCM:methanol:ammonia (80:20:2) to give the title compound (11.31 g) in a 45% yield.

후처리

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue was partitioned between EtOAc (400 mL) and saturated sodium hydrogen carbonate aqueous solution (300 mL)
  3. washThe organic layer was washed with further saturated sodium hydrogen carbonate aqueous solution (300 mL)
  4. extractionThe combined aqueous layers were re-extracted with EtOAc (400 mL)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by column chromatography on silica gel eluting with DCM:methanol:ammonia (80:20:2)

출처 및 근거

ORD 기록
ord-640b9a18d261461f9c78e5e0a37bcaff
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08575336B2

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