4-(Bromomethyl)-2,2-dimethyl-1,3-dioxolane → N-(1-((1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-5-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 79280

Reaktionsgleichung

Reaktionsgleichung von HRID 79280
[NH:1]1[CH:5]=[CH:4][C:3]([CH2:6][N:7]2[C:15]3[C:10](=[C:11]([NH:16][C:17]([C:19]4[N:23]5[CH:24]=[CH:25][CH:26]=[CH:27][C:22]5=[N:21][CH:20]=4)=[O:18])[CH:12]=[CH:13][CH:14]=3)[C:9]([CH2:28][CH3:29])=[N:8]2)=[N:2]1.Br[CH2:31][CH:32]1[CH2:36][O:35][C:34]([CH3:38])([CH3:37])[O:33]1.O.[OH-].[Cs+]>CN(C)C=O>[CH3:37][C:34]1([CH3:38])[O:33][CH:32]([CH2:31][N:2]2[C:3]([CH2:6][N:7]3[C:15]4[C:10](=[C:11]([NH:16][C:17]([C:19]5[N:23]6[CH:24]=[CH:25][CH:26]=[CH:27][C:22]6=[N:21][CH:20]=5)=[O:18])[CH:12]=[CH:13][CH:14]=4)[C:9]([CH2:28][CH3:29])=[N:8]3)=[CH:4][CH:5]=[N:1]2)[CH2:36][O:35]1

Komponenten

5

Edukt 3

HCID 1697594-(Bromomethyl)-2,2-dimethyl-1,3-dioxolaneHCID 23679066Caesium hydroxide--water (1/1/1)HCID 178437952HCID 178437952, Verbindung

Produkt 1

HCID 67260734N-(1-((1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-5-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of N-(1-((1H-pyrazol-3-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (40 mg, 0.104 mmol) in N,N-dimethylformamide (0.5 mL) was added 4-(bromomethyl)-2,2-dimethyl-1,3-dioxolane (20.2 mg, 0.104 mmol) and cesium hydroxide hydrate (17.4 mg, 0.104 mmol). The mixture was stirred for 16 hours at ambient temperature, filtered, washing with methanol and ethyl acetate, and concentrated under a stream of nitrogen. The resulting material was purified using preparative thin layer chromatography on silica, eluting with 10% methanol in dichloromethane. The isolated product (22.5 mg) was a 7:3 mixture of two regioisomers, N-(1-((1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-5-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide and N-(1-((1-(2,3-dihydroxypropyl)-1H-pyrazol-3-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide. This material was continued to the next step as a mixture.

Aufarbeitung

  1. filtrationfiltered
  2. washwashing with methanol and ethyl acetate
  3. concentrationconcentrated under a stream of nitrogen
  4. customThe resulting material was purified
  5. washeluting with 10% methanol in dichloromethane
  6. additiona 7:3 mixture of two regioisomers, N-(1-((1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-5-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide and N-(1-((1-(2,3-dihydroxypropyl)-1H-pyrazol-3-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

Quellen und Nachweise

ORD-Eintrag
ord-bca7df72b6594554ae61604e328be30f
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08841455B2

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