Dichloromethane → 6-(5-chloro-2-fluoropyridin-4-yl)-3-methyl-N-(tetrahydro-2H-pyran-4-yl-methyl)pyrazine-2-amine

HRID 1623338ノート

反応式

HRID 1623338 の反応式
Cl[C:2]1[C:3]([NH:16][CH2:17][CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[N:4][C:5]([C:8]2[C:13]([Cl:14])=[CH:12][N:11]=[C:10]([F:15])[CH:9]=2)=[CH:6][N:7]=1.[CH3:24]B(O)O.C(=O)([O-])[O-].[Na+].[Na+].C(Cl)Cl>COCCOC>[Cl:14][C:13]1[C:8]([C:5]2[N:4]=[C:3]([NH:16][CH2:17][CH:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[C:2]([CH3:24])=[N:7][CH:6]=2)=[CH:9][C:10]([F:15])=[N:11][CH:12]=1

参加物

6

反応物 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 139377Methylboronic AcidHCID 866506283-chloro-6-(5-chloro-2-fluoropyridin-4-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine

生成物 1

HCID 669371456-(5-chloro-2-fluoropyridin-4-yl)-3-methyl-N-(tetrahydro-2H-pyran-4-yl-methyl)pyrazine-2-amine収率 191.6%

試薬・触媒・溶媒 1

HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
105 °C

実験手順

3-chloro-6-(5-chloro-2-fluoropyridin-4-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine (0.0275 g, 0.077 mmol), methylboronic acid (0.014 g, 0.231 mmol), and sodium carbonate (0.100 ml, 0.200 mmol, 2M aq solution) were dissolved in DME (1.0 ml). The solution was then degassed by sparging with argon for 5 min. It was then treated with PdCl2(dppf).CH2Cl2 adduct (0.013 g, 0.015 mmol). The reaction mixture was then heated in the microwave at 105° C. for 20 min. More of the above reagents in the same amounts were added to the reaction mixture and heating in the microwave was continued at 115° C. for 20 min. The reaction mixture was allowed to cool to ambient temperature. It was then filtered through a pad of Celite. The filtrate was concentrated in vacuo to yield 0.0497 g of a mixture of 6-(5-chloro-2-fluoropyridin-4-yl)-3-methyl-N-((tetrahydro-2H-pyran-4-yl)pyrazine-2-amine and 6-(2-fluoro-5-methylpyridin-4-yl)-3-methyl-N-((tetrahydro-2H-pyran-4-yl_methyl)pyrazine-2-amine.

後処理

  1. customThe solution was then degassed
  2. customby sparging with argon for 5 min
  3. additionIt was then treated with PdCl2(dppf)
  4. additionMore of the above reagents in the same amounts were added to the reaction mixture
  5. temperatureheating in the microwave
  6. temperatureto cool to ambient temperature
  7. filtrationIt was then filtered through a pad of Celite
  8. concentrationThe filtrate was concentrated in vacuo

出典と根拠

ORDレコード
ord-97a8cac069334d96bca3f591ef6d8eec
出典データセット
uspto-grants-2014_07
特許番号
US08778951B2

反応ノート

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