p-Toluenesulfonic acid → 2-(4-((4-((4-cyano-2,6-difluorobenzyl)amino)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)-N-isopropylacetamide

HRID 929909ノート

反応式

HRID 929909 の反応式
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:10]=[N:11][N:12]([CH2:14][C:15]([NH:17][CH:18]([CH3:20])[CH3:19])=[O:16])[CH:13]=2)[N:3]=1.[NH2:21][CH2:22][C:23]1[C:30]([F:31])=[CH:29][C:26]([C:27]#[N:28])=[CH:25][C:24]=1[F:32].CC1C=CC(S(O)(=O)=O)=CC=1>O1CCOCC1>[C:27]([C:26]1[CH:25]=[C:24]([F:32])[C:23]([CH2:22][NH:21][C:2]2[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]3[CH:10]=[N:11][N:12]([CH2:14][C:15]([NH:17][CH:18]([CH3:20])[CH3:19])=[O:16])[CH:13]=3)[N:3]=2)=[C:30]([F:31])[CH:29]=1)#[N:28]

参加物

5

反応物 3

HCID 6101p-Toluenesulfonic acidHCID 219055604-(Aminomethyl)-3,5-difluorobenzonitrileHCID 900240272-(4-(4-chloropyrimidin-2-ylamino)-1H-pyrazol-1-yl)-N-isopropylacetamide

生成物 1

HCID 727064692-(4-((4-((4-cyano-2,6-difluorobenzyl)amino)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)-N-isopropylacetamide

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

実験手順

A solution of 2-(4-(4-chloropyrimidin-2-ylamino)-1H-pyrazol-1-yl)-N-isopropylacetamide (120 mg, 0.41 mmol) (II-1, prepared by Procedure D), 4-(aminomethyl)-3,5-difluorobenzonitrile (68 mg, 0.41 mmol) (III-1, prepared by Procedure E) and TsOH (56 mg, 0.33 mmol) in dioxane (2 mL) was heated to 160° C. for 2 h then concentrated in vacuo. The residue was dissolved in ethyl acetate, washed with Na2CO3(aq), dried (Na2SO4), concentrated in vacuo and purified by prep. TLC (5-10% v/v MeOH/DCM) to afford 2-(4-((4-((4-cyano-2,6-difluorobenzyl)amino)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)-N-isopropylacetamide I-1 (50 mg, 29%) as a white solid. LC-MS (Method A), RT=8.02 min. (ES+) 427.

後処理

  1. concentrationthen concentrated in vacuo
  2. dissolutionThe residue was dissolved in ethyl acetate
  3. washwashed with Na2CO3(aq)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. custompurified by prep

出典と根拠

ORDレコード
ord-a6ef61f3edfd4753a41c7eadd4cdf7cc
出典データセット
uspto-grants-2016_03
特許番号
US09296725B2

反応ノート

読み込み中…