Methyl iodide → 5-({[1-Methyl-4-oxo-5-(5-pyrimidinylmethyl)-1,4-dihydro-2-pyrimidinyl]thio}methyl)-2-{[3-(trifluoromethyl)phenyl]oxy}benzonitrile

HRID 706058ノート

反応式

HRID 706058 の反応式
[N:1]1[CH:6]=[C:5]([CH2:7][C:8]2[C:9](=[O:15])[NH:10][C:11](=[S:14])[NH:12][CH:13]=2)[CH:4]=[N:3][CH:2]=1.[CH3:16]CN(C(C)C)C(C)C.Cl[CH2:26][C:27]1[CH:28]=[CH:29][C:30]([O:35][C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([C:42]([F:45])([F:44])[F:43])[CH:37]=2)=[C:31]([CH:34]=1)[C:32]#[N:33].CI>C(Cl)Cl.[Zn+2].[Br-].[Br-].CN1C(=O)CCC1>[CH3:16][N:12]1[CH:13]=[C:8]([CH2:7][C:5]2[CH:6]=[N:1][CH:2]=[N:3][CH:4]=2)[C:9](=[O:15])[N:10]=[C:11]1[S:14][CH2:26][C:27]1[CH:28]=[CH:29][C:30]([O:35][C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([C:42]([F:45])([F:44])[F:43])[CH:37]=2)=[C:31]([CH:34]=1)[C:32]#[N:33]

参加物

8

反応物 4

HCID 6328Methyl iodideHCID 81531Diisopropylethylamine2 回HCID 109660395-(Pyrimid-5-ylmethyl)-2-thiouracilHCID 668253585-(Chloromethyl)-{[3-(trifluoromethyl)phenyl]oxy}benzonitrile

生成物 1

HCID 677748475-({[1-Methyl-4-oxo-5-(5-pyrimidinylmethyl)-1,4-dihydro-2-pyrimidinyl]thio}methyl)-2-{[3-(trifluoromethyl)phenyl]oxy}benzonitrile収率 9.8%

試薬・触媒・溶媒 3

HCID 10421208Zinc bromide触媒HCID 6344Dichloromethane溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
60 °C

実験手順

To a solution of 5-(5-pyrimidinylmethyl)-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone (70.7 mg, 0.321 mmol) and DIPEA (0.084 ml, 0.481 mmol) in DCM (2 ml) was added 5-(chloromethyl)-2-{[3-(trifluoromethyl)phenyl]oxy}benzonitrile (100 mg, 0.321 mmol). The reaction mixture was heated at 60° C. overnight. After removing the solvent by nitrogen, the residue was dissolved in MeCN (4 ml), and NMP (1.5 ml), and ZnBr2 (107 mg, 0.477 mmol) and DIPEA (0.083 ml, 0.477 mmol) were added. The mixture was then stirred at 60° C. for 10 min. And MeI (0.022 mL, 0.353 mmol) was added dropwise, then stirred at 60° C. for 1.5 h. Purification via MDAP then afforded the title compound (16 mg, 8.01% yield). LCMS: rt=2.96 min, [M+H+]=510

後処理

  1. customAfter removing the solvent by nitrogen
  2. dissolutionthe residue was dissolved in MeCN (4 ml)
  3. stirringstirred at 60° C. for 1.5 h
  4. customPurification via MDAP

出典と根拠

ORDレコード
ord-add684ebc093427ab455af220df84ff8
出典データセット
uspto-grants-2015_11
特許番号
US09174968B2

反応ノート

読み込み中…