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Acetyl chloride → N-(5-(4-acetylpiperazin-1-yl)-2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)phenyl)acrylamide

HRID 58195
ノート
印刷プレビュー

反応式

HRID 58195 の反応式
[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([O:10][CH3:11])=[C:4]([Cl:12])[C:3]=1[NH:13][C:14](=[O:41])[N:15]([C:17]1[N:22]=[CH:21][N:20]=[C:19]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([N:30]3[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]3)=[CH:26][C:25]=2[NH:36][C:37](=[O:40])[CH:38]=[CH2:39])[CH:18]=1)[CH3:16].CCN(C(C)C)C(C)C.[C:51](Cl)(=[O:53])[CH3:52]>C(Cl)Cl>[C:51]([N:33]1[CH2:32][CH2:31][N:30]([C:27]2[CH:28]=[CH:29][C:24]([NH:23][C:19]3[CH:18]=[C:17]([N:15]([CH3:16])[C:14]([NH:13][C:3]4[C:2]([Cl:1])=[C:7]([O:8][CH3:9])[CH:6]=[C:5]([O:10][CH3:11])[C:4]=4[Cl:12])=[O:41])[N:22]=[CH:21][N:20]=3)=[C:25]([NH:36][C:37](=[O:40])[CH:38]=[CH2:39])[CH:26]=2)[CH2:35][CH2:34]1)(=[O:53])[CH3:52]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 118025964N-(2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)-5-(piperazin-1-yl)phenyl)acrylamide

生成物 1

HCID 118026272N-(5-(4-acetylpiperazin-1-yl)-2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)phenyl)acrylamide収率 15.5%

試薬・触媒・溶媒 1

HCID 6344
Dichloromethane
溶媒
2 回

実験手順

N-(2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)-5-(piperazin-1-yl)phenyl)acrylamide (Procedure 2L, Example 157) (8.6 g, 0.014 mmol) and DIEA (7.5 μl, 0.043 mmol) were stirred in DCM (1.0 ml) at room temperature under nitrogen atmosphere. A solution of acetyl chloride (1.0 μl, 0.016 mmol) in DCM (11 ul) was added and the reaction mixture was stirred at room temperature for 2 hours. The solvent was evaporated and the resulting material was dissolved in 400 ul of DMSO. The DMSO solution was diluted with 1.0 ml of MeOH and purified by prep-HPLC (water/ACN in formic acid condition) to afford the title compound (1.4 mg, yield: 15%). 1H-NMR (400 MHz, MeOH-d4) δ 2.16 (s, 3H) 3.65-3.80 (m, 4H) 3.94 (s, 6H) 5.76 (dd, 1H) 6.15 (s, 1H) 6.28-6.49 (m, 2H) 6.78-6.82 (m, 1H) 6.95 (dd, 2.89 Hz, 1H) 7.28-7.38 (m, 2H) 8.31 (d, 1H) 8.58 (br. s., 1H); ESI-MS: 643 [M+H]+.

後処理

  1. customThe solvent was evaporated
  2. dissolutionthe resulting material was dissolved in 400 ul of DMSO
  3. additionThe DMSO solution was diluted with 1.0 ml of MeOH
  4. custompurified by prep-HPLC (water/ACN in formic acid condition)

出典と根拠

ORDレコード
ord-db20c3b4ce4b4cafa48b51f90300dd55
出典データセット
uspto-grants-2016_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09434697B2

反応ノート

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