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 706048노트

반응식

HRID 706048 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][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]

참가 물질

8

반응물 4

HCID 6328Methyl iodideHCID 81531Diisopropylethylamine2회HCID 109660395-(Pyrimid-5-ylmethyl)-2-thiouracilHCID 677735002-(4-Chloro-3-(trifluoromethyl)phenoxy)-5-(chloromethyl)benzonitrile

생성물 1

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

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 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

후처리

  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

출처 및 근거

ORD 기록
ord-db52d03d7c7e49669687b2abc67697dc
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09174968B2

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