Diisopropylethylamine → N-{5-chloro-2-{[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]amino}-6-[(5-methoxy-1H-pyrazol-3-yl)amino]pyrimidin-4-yl}-N,N',N'-trimethylsulfamide

HRID 415404ノート

反応式

HRID 415404 の反応式
Cl[C:2]1[N:7]=[C:6]([N:8]([CH3:15])[S:9]([N:12]([CH3:14])[CH3:13])(=[O:11])=[O:10])[C:5]([Cl:16])=[C:4]([NH:17][C:18]2[CH:22]=[C:21]([O:23][CH3:24])[NH:20][N:19]=2)[N:3]=1.Cl.[F:26][C:27]1[CH:28]=[N:29][C:30]([C@@H:33]([NH2:35])[CH3:34])=[N:31][CH:32]=1.CCN(C(C)C)C(C)C>CCCCO>[Cl:16][C:5]1[C:6]([N:8]([CH3:15])[S:9]([N:12]([CH3:14])[CH3:13])(=[O:11])=[O:10])=[N:7][C:2]([NH:35][C@H:33]([C:30]2[N:31]=[CH:32][C:27]([F:26])=[CH:28][N:29]=2)[CH3:34])=[N:3][C:4]=1[NH:17][C:18]1[CH:22]=[C:21]([O:23][CH3:24])[NH:20][N:19]=1

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 66624037(S)-1-(5-Fluoropyrimidin-2-yl)ethanamine hydrochlorideHCID 178493077HCID 178493077、化合物

生成物 1

HCID 178493099N-{5-chloro-2-{[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]amino}-6-[(5-methoxy-1H-pyrazol-3-yl)amino]pyrimidin-4-yl}-N,N',N'-trimethylsulfamide収率 87%

試薬・触媒・溶媒 1

HCID 2631-Butanol溶媒

反応条件

温度
160 °C

実験手順

A microwave reaction vessel was charged with N-{2,5-dichloro-6-[(5-methoxy-1H-pyrazol-3-yl)amino]pyrimidin-4-yl}-N,N′,N′-trimethylsulfamide (Method 29, 44.1 mg, 0.112 mmol), (S)-1-(5-fluoropyrimidin-2-yl)ethanamine hydrochloride (Method 7, 39.5 mg, 0.223 mmol), and DIPEA (0.062 ml, 0.352 mmol). Anhydrous n-BuOH (1 ml) was added, and the tube was sealed and heated in a microwave reactor at 160° C. for 2 hours. The reaction mixture was purified by silica gel chromatography (by ISCO Combiflash with gradient EtOAc and hexane) to afford the title compound as a white solid (48.6 mg, 87%). LC-MS, 501 (M+1). 1H NMR (DMSO-d6, 400 MHz) δ 12.01 (s, 1H), 9.76 (s, 1H), 8.83 (s, 2H), 8.21 (s, 1H), 5.60 (s, 1H), 5.04-5.06 (m, 1H), 3.76 (s, 3H), 2.80 (s, 3H), 2.70 (s, 6H), 1.59 (d, 3H).

後処理

  1. customA microwave reaction vessel
  2. customthe tube was sealed
  3. customThe reaction mixture was purified by silica gel chromatography (by ISCO Combiflash with gradient EtOAc and hexane)

出典と根拠

ORDレコード
ord-531af947ec434708a9b3ab556f397bea
出典データセット
uspto-grants-2012_01
特許番号
US08088784B2

反応ノート

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