Acetic Acid → 5-(1-Benzyl-piperidin-3-ylamino)-indazole-1-carboxylic acid tert-butyl ester

HRID 1520232

反応式

HRID 1520232 の反応式
Cl.[CH2:2]([N:9]1[CH2:14][CH2:13][CH2:12][C:11](=O)[CH2:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:16]([O:20][C:21]([N:23]1[C:31]2[C:26](=[CH:27][C:28]([NH2:32])=[CH:29][CH:30]=2)[CH:25]=[N:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17].CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[C:16]([O:20][C:21]([N:23]1[C:31]2[C:26](=[CH:27][C:28]([NH:32][CH:11]3[CH2:12][CH2:13][CH2:14][N:9]([CH2:2][C:3]4[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=4)[CH2:10]3)=[CH:29][CH:30]=2)[CH:25]=[N:24]1)=[O:22])([CH3:19])([CH3:17])[CH3:18]

参加物

7

反応物 4

HCID 176Acetic AcidHCID 30849241-Benzyl-3-piperidone hydrochloride hydrateHCID 5049666Sodium triacetoxyborohydrideHCID 198005561,1-Dimethylethyl 5-amino-1H-indazole-1-carboxylate

生成物 1

HCID 709792425-(1-Benzyl-piperidin-3-ylamino)-indazole-1-carboxylic acid tert-butyl ester収率 75%

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
30 °C

実験手順

A mixture of 1-benzyl-piperidin-3-one hydrochloride (116 g, 0.52 mol, 1.2 eq) and TEA (43.5 g, 0.43 mol, 1.0 eq) in DCE (800 ml) was stirred at 30° C. for 1 hr. Then 5-amino-indazole-1-carboxylic acid tert-butyl ester (100 g, 0.43 mol, 1.0 eq) and CH3COOH (25.8 g, 0.43 mol, 1.0 eq) were added to the reaction mixture NaBH(OAc)3 (273 g, 1.29 mol, 3.0 eq) was added in one portion after 30 min. The mixture was stirred at 30° C. for 16 hrs. LC-MS showed the reaction was complete. 1 L DCM was added to the reaction mixture and the organic layer was washed with saturated. NaHCO3 (800 ml*3) and H2O (500 ml*3), dried over Na2SO4 and concentrated by rotavapor. The crude product was purified by column chromatography on silica gel using DCM: CH3OH=60:1 to give the 5-(1-benzyl-piperidin-3-ylamino)-indazole-1-carboxylic acid tert-butyl ester (131 g, 75%).

後処理

  1. additionwas added in one portion after 30 min
  2. stirringThe mixture was stirred at 30° C. for 16 hrs
  3. washthe organic layer was washed with saturated
  4. dry with materialNaHCO3 (800 ml*3) and H2O (500 ml*3), dried over Na2SO4
  5. concentrationconcentrated by rotavapor
  6. customThe crude product was purified by column chromatography on silica gel

出典と根拠

ORDレコード
ord-0fe16e2950ee4a7da50c2cdf24589b11
出典データセット
uspto-grants-2015_07
特許番号
US09073905B2

関連ノート

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