N-methyl-2-pyrrolidone → 1-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-piperidine-4-carboxylic acid methyl ester

HRID 216269

反応式

HRID 216269 の反応式
[CH3:1][O:2][C:3]([CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:16]=[C:15](Cl)[N:14]=[C:13]([O:18][CH3:19])[N:12]=2)[CH2:7][CH2:6]1)=[O:4].[Cl:20][C:21]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=1[CH2:28][CH2:29][NH2:30].C(=O)(O)[O-].[Na+].CN1CCCC1=O>O>[CH3:1][O:2][C:3]([CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:16]=[C:15]([NH:30][CH2:29][CH2:28][C:22]3[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:21]=3[Cl:20])[N:14]=[C:13]([O:18][CH3:19])[N:12]=2)[CH2:7][CH2:6]1)=[O:4]

参加物

6

反応物 4

HCID 13387N-methyl-2-pyrrolidoneHCID 1429382,4-Dichlorophenethylamine2 回HCID 516892Sodium BicarbonateHCID 866157151-(6-Chloro-2-methoxy-pyrimidin-4-yl)-piperidine-4-carboxylic acid methyl ester

生成物 1

HCID 690694161-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-piperidine-4-carboxylic acid methyl ester収率 44.3%

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
140 °C

実験手順

In a tube is combined 1-(6-chloro-2-methoxy-pyrimidin-4-yl)-piperidine-4-carboxylic acid methyl ester [103 mg, 0.36 mmol], 2-(2,4-dichloro-phenyl)-ethylamine (0.163 mL, 1.08 mmol), sodium bicarbonate (181 mg, 2.16 mmol) and N-methylpyrrolidinone (2 mL). The mixture is heated at 140° C. for 12 h. Additional 2-(2,4-dichloro-phenyl)-ethylamine (0.2 mL, 1.33 mmol) is added and heating at 140° C. is continued for another 12 h. The mixture is diluted with water (30 mL) and extracted twice with EtOAc (30 mL). The organic extracts are washed twice with water (40 mL) and once with brine (30 mL), combined, dried over magnesium sulfate, filtered and concentrated. The residue is subjected to chromatography on silica gel eluting with 40% ethyl acetate:heptane to afford 1-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-piperidine-4-carboxylic acid methyl ester [70 mg, 44%] as a solid.

後処理

  1. customIn a tube is combined
  2. temperatureheating at 140° C.
  3. extractionextracted twice with EtOAc (30 mL)
  4. washThe organic extracts are washed twice with water (40 mL) and once with brine (30 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

出典と根拠

ORDレコード
ord-247c3aba7db44a629a0d1f8a468a55a0
出典データセット
uspto-grants-2012_06
特許番号
US08193183B2

関連ノート

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