Hydrochloric Acid → 2-(5-amino-4,6-dimethylpyrimidine-2-yloxy)-N-(1-(cyclopropylmethyl)piperidine-4-yl)-N-methylacetamide

HRID 1749300

Reaktionsgleichung

Reaktionsgleichung von HRID 1749300
[CH:1]1([CH2:4][N:5]2[CH2:10][CH2:9][CH:8]([N:11]([CH3:32])[C:12](=[O:31])[CH2:13][O:14][C:15]3[N:20]=[C:19]([CH3:21])[C:18]([NH:22]C(=O)OC(C)(C)C)=[C:17]([CH3:30])[N:16]=3)[CH2:7][CH2:6]2)[CH2:3][CH2:2]1.Cl.[OH-].[Na+]>C(Cl)(Cl)Cl>[NH2:22][C:18]1[C:19]([CH3:21])=[N:20][C:15]([O:14][CH2:13][C:12]([N:11]([CH:8]2[CH2:9][CH2:10][N:5]([CH2:4][CH:1]3[CH2:3][CH2:2]3)[CH2:6][CH2:7]2)[CH3:32])=[O:31])=[N:16][C:17]=1[CH3:30]

Komponenten

5

Edukt 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 59336181Tert-butyl 2-(2-((1-(cyclopropylmethyl)-piperidine-4-yl)(methyl)amino)-2-oxoethoxy)-4,6-dimethylpyrimidine-5-ylcarbamate

Produkt 1

HCID 251208412-(5-amino-4,6-dimethylpyrimidine-2-yloxy)-N-(1-(cyclopropylmethyl)piperidine-4-yl)-N-methylacetamideAusbeute 62 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6212ChloroformLösungsmittel

Versuchsvorschrift

To a chloroform (1 mL) solution of Compound 49 (78 mg), 6N HCl (1 mL) was added and the mixture was stirred at room temperature for 1 hour. While the reaction mixture was cooled with ice, a 4N aqueous sodium hydroxide solution was added to neutralize the mixture. The resulting product was extracted with chloroform and the organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by amino-coated silica gel (Fuji Sylysia Chemical Ltd.; NH-DM1020) column chromatography (ethyl acetate) to give 37.5 mg (62% yield) of 2-(5-amino-4,6-dimethylpyrimidine-2-yloxy)-N-(1-(cyclopropylmethyl)piperidine-4-yl)-N-methylacetamide. Then, to a methanol solution of 2-(5-amino-4,6-dimethylpyrimidine-2-yloxy)-N-(1-(cyclopropylmethyl)piperidine-4-yl)-N-methylacetamide, 2 equivalents of 4N HCl/1,4-dioxane solution was added and the mixture was concentrated under reduced pressure. The desired product was afforded by recrystallization from methanol/ethyl acetate as white crystals.

Aufarbeitung

  1. temperatureWhile the reaction mixture was cooled with ice
  2. extractionThe resulting product was extracted with chloroform
  3. dry with materialthe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by amino-coated silica gel (Fuji Sylysia Chemical Ltd.; NH-DM1020) column chromatography (ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-044807e391644d669d904a589ea8fe71
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09156817B2

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