Diisopropylethylamine → 2-{6-(4-Chloro-benzyl)-2-[1-(6-methyl-pyrimidin-4-yl)-piperidin-4-ylamino]-pyrimidin-4-yl}-propan-2-ol

HRID 451415ノート

反応式

HRID 451415 の反応式
Cl.Cl.[CH3:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]([N:10]2[CH2:15][CH2:14][CH:13]([NH2:16])[CH2:12][CH2:11]2)[CH:5]=1.C(N(CC)C(C)C)(C)C.Cl[C:27]1[N:32]=[C:31]([C:33]([OH:36])([CH3:35])[CH3:34])[CH:30]=[C:29]([CH2:37][C:38]2[CH:43]=[CH:42][C:41]([Cl:44])=[CH:40][CH:39]=2)[N:28]=1>CN1CCCC1=O.O1CCOCC1.O>[Cl:44][C:41]1[CH:42]=[CH:43][C:38]([CH2:37][C:29]2[N:28]=[C:27]([NH:16][CH:13]3[CH2:14][CH2:15][N:10]([C:6]4[CH:5]=[C:4]([CH3:3])[N:9]=[CH:8][N:7]=4)[CH2:11][CH2:12]3)[N:32]=[C:31]([C:33]([OH:36])([CH3:35])[CH3:34])[CH:30]=2)=[CH:39][CH:40]=1

参加物

7

反応物 3

HCID 81531DiisopropylethylamineHCID 673421331-(6-Methylpyrimidin-4-yl)piperidin-4-amine dihydrochlorideHCID 866567012-[2-Chloro-6-(4-chloro-benzyl)-pyrimidin-4-yl]-propan-2-ol

生成物 1

HCID 533533392-{6-(4-Chloro-benzyl)-2-[1-(6-methyl-pyrimidin-4-yl)-piperidin-4-ylamino]-pyrimidin-4-yl}-propan-2-ol

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 13387N-methyl-2-pyrrolidone溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
160 °C

実験手順

To a solution of 1-(6-methyl-pyrimidin-4-yl)-piperidin-4-ylamine dihydrochloride (53 mg, 0.2 mmol) and N,N-diisopropylethyl amine (120 L, 0.7 mmol) in N-methyl-pyrrolidinone (0.5 mL) was added a solution of 2-[2-chloro-6-(4-chloro-benzyl)-pyrimidin-4-yl]-propan-2-ol (65.4 mg, 0.22 mmol)) in dioxane (1.5 mL). The reaction was heated at 160° C. in a microwave oven for 5 hours. The reaction was diluted with water and extracted twice with ethyl acetate. The combined organic layers were washed with water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using a gradient from AcOEt to AcOEt/EtOH 9:1 (v/v) as eluent. The title compound was obtained as a white solid (27 mg, 30%).

後処理

  1. extractionextracted twice with ethyl acetate
  2. washThe combined organic layers were washed with water
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography on silica gel using a gradient from AcOEt to AcOEt/EtOH 9:1 (v/v) as eluent

出典と根拠

ORDレコード
ord-649f495cb4e046c3b1dc68efbc5e8599
出典データセット
uspto-grants-2013_07
特許番号
US08486967B2

反応ノート

読み込み中…