Sodium hydride → HCID 71554399、化合物

HRID 1776404ノート

反応式

HRID 1776404 の反応式
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]2[N:15]=[C:14]([NH:16][C:17]3[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=3)[C:13]([O:23][CH3:24])=[CH:12][N:11]=2)=[N:2]1.[H-].[Na+].Br[CH2:28][C:29]1[C:34]([F:35])=[C:33]([CH3:36])[CH:32]=[CH:31][C:30]=1[Cl:37]>O1CCCC1>[Cl:37][C:30]1[C:29]([CH2:28][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3]([C:10]3[N:15]=[C:14]([NH:16][C:17]4[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=4)[C:13]([O:23][CH3:24])=[CH:12][N:11]=3)=[N:2]2)=[C:34]([F:35])[C:33]([CH3:36])=[CH:32][CH:31]=1

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 27736806-Chloro-2-fluoro-3-methylbenzyl bromideHCID 86732418HCID 86732418、化合物

生成物 1

HCID 71554399HCID 71554399、化合物

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

80 mg of 2-(1H-indazol-3-yl)-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amine (1-6-1, 0.251 mmol, 1. eq.) were suspended in dry tetrahydrofuran under a nitrogen atmosphere. 30.2 mg of sodium hydride (60% purity) were added and stirred at room temperature for 10 minutes. Then 59.7 mg of 2-(bromomethyl)-1-chloro-3-fluoro-4-methylbenzene were added. The reaction mixture was stirred for 18 hours at room temperature. Then the mixture was partitioned between half saturated aq. ammonium chloride solution and dichloromethane/isopropanol 4:1. The phases were separated and the aqueous layer was extracted twice with dichloromethane/isopropanol 4:1. The combined organic layers were washed with brine, dried over a silicone filter and concentrated in vacuo. Preparative HPLC purification provided 29 mg (0.06 mmol, 24.1%) of the analytically pure target compound.

後処理

  1. stirringThe reaction mixture was stirred for 18 hours at room temperature
  2. customThen the mixture was partitioned between half saturated aq. ammonium chloride solution and dichloromethane/isopropanol 4:1
  3. customThe phases were separated
  4. extractionthe aqueous layer was extracted twice with dichloromethane/isopropanol 4:1
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over a silicone
  7. filtrationfilter
  8. concentrationconcentrated in vacuo
  9. customPreparative HPLC purification
  10. customprovided 29 mg (0.06 mmol, 24.1%) of the analytically pure target compound

出典と根拠

ORDレコード
ord-c19c810e7380487cb1d26dc2c0dfd5c5
出典データセット
uspto-grants-2016_02
特許番号
US09265763B2

反応ノート

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