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

HRID 474824노트

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HRID 474824 반응식
[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]

참가 물질

8

반응물 4

HCID 6328Methyl iodideHCID 81531Diisopropylethylamine2회HCID 109660395-(Pyrimid-5-ylmethyl)-2-thiouracilHCID 668253585-(Chloromethyl)-{[3-(trifluoromethyl)phenyl]oxy}benzonitrile

생성물 1

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

시약·촉매·용매 3

HCID 10421208Zinc bromide촉매HCID 6344Dichloromethane용매HCID 13387N-methyl-2-pyrrolidone용매

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온도
60 °C

실험 절차

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

후처리

  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

출처 및 근거

ORD 기록
ord-2c8b0243af8c44e2a68bddd6d1ccab52
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637536B2

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