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

HRID 1054024

Reaktionsgleichung

Reaktionsgleichung von HRID 1054024
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]

Komponenten

7

Edukt 4

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
30 °C

Versuchsvorschrift

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%).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-ddb46d42fcd240a89dedebb92b1c59a3
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09394286B2

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