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

HRID 706048ノート

反応式

HRID 706048 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][C:39]([Cl:42])=[C:38]([C:43]([F:46])([F:45])[F:44])[CH:37]=2)=[C:31]([CH:34]=1)[C:32]#[N:33].CI>C(Cl)Cl.[Zn+2].[Br-].[Br-].CN1C(=O)CCC1>[Cl:42][C:39]1[CH:40]=[CH:41][C:36]([O:35][C:30]2[CH:29]=[CH:28][C:27]([CH2:26][S:14][C:11]3[N:12]([CH3:16])[CH:13]=[C:8]([CH2:7][C:5]4[CH:6]=[N:1][CH:2]=[N:3][CH:4]=4)[C:9](=[O:15])[N:10]=3)=[CH:34][C:31]=2[C:32]#[N:33])=[CH:37][C:38]=1[C:43]([F:46])([F:45])[F:44]

参加物

8

反応物 4

HCID 6328Methyl iodideHCID 81531Diisopropylethylamine2 回HCID 109660395-(Pyrimid-5-ylmethyl)-2-thiouracilHCID 677735002-(4-Chloro-3-(trifluoromethyl)phenoxy)-5-(chloromethyl)benzonitrile

生成物 1

HCID 677755592-{[4-Chloro-3-(trifluoromethyl)phenyl]oxy}-5-({[1-methyl-4-oxo-5-(5-pyrimidinylmethyl)-1,4-dihydro-2-pyrimidinyl]thio}methyl)benzonitrile収率 13.9%

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 mg, 0.318 mmol) and DIPEA (0.083 ml, 0.477 mmol) in DCM (2 ml), was added 5-(chloromethyl)-2-{[4-chloro-3-(trifluoromethyl)phenyl]oxy}benzonitrile (110 mg, 0.318 mmol). The mixture was stirred 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 heated at 60° C. for 10 min. And MeI (0.020 ml, 0.318 mmol) was added dropwise, then stirred at 60° C. for 1.5 h. Purification via MDAP then afforded the title compound (24 mg, 11.49% yield). LCMS: rt=3.20 min, [M+H+]=544

後処理

  1. customAfter removing the solvent by nitrogen
  2. dissolutionthe residue was dissolved in MeCN (4 ml)
  3. temperatureThe mixture was then heated at 60° C. for 10 min
  4. stirringstirred at 60° C. for 1.5 h
  5. customPurification via MDAP

出典と根拠

ORDレコード
ord-db52d03d7c7e49669687b2abc67697dc
出典データセット
uspto-grants-2015_11
特許番号
US09174968B2

反応ノート

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