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

HRID 2280930

反応式

HRID 2280930 の反応式
[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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6212Chloroform溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-2c36671e866f4464b62ef24857dafdda
出典データセット
uspto-grants-2015_09
特許番号
US09139559B2

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