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

HRID 1054024Notes

Reaction equation

HRID 1054024 reaction equation
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]

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
30 °C

Procedure

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 hour. 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 and the reaction mixture stirred for 30 min. NaBH(OAc)3 (273 g, 1.29 mol, 3.0 eq) was then added in one portion and the mixture stirred at 30° C. for 16 hours. LC-MS showed complete conversion. The reaction mixture was diluted in DCM (1 L) and the organic layer washed with saturated NaHCO3 (800 mL×3) and H2O (500 mL×3), dried over Na2SO4 and concentrated under vacuum. The crude product was purified by column chromatography on silica gel using (DCM:MeOH=60:1) to give the 5-(1-benzyl-piperidin-3-ylamino)-indazole-1-carboxylic acid tert-butyl ester (131 g, 75%).

Workup

  1. stirringthe reaction mixture stirred for 30 min
  2. stirringthe mixture stirred at 30° C. for 16 hours
  3. washthe organic layer washed with saturated NaHCO3 (800 mL×3) and H2O (500 mL×3)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under vacuum
  6. customThe crude product was purified by column chromatography on silica gel using (DCM:MeOH=60:1)

Sources & evidence

ORD record
ord-ddb46d42fcd240a89dedebb92b1c59a3
Source dataset
uspto-grants-2016_07
Patent number
US09394286B2

Reaction notes

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