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 340062

反応式

HRID 340062 の反応式
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

参加物

5

反応物 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

生成物 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-carboxamidine収率 45%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒2 回

反応条件

温度
50 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-30de459a267648bc9036f222bbffa809
出典データセット
uspto-grants-2014_11
特許番号
US08895544B2

関連ノート

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