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
Reaction equation
[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]Participants
8
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 60 °C
Procedure
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
Workup
- customAfter removing the solvent by nitrogen
- dissolutionthe residue was dissolved in MeCN (4 ml)
- temperatureThe mixture was then heated at 60° C. for 10 min
- stirringstirred at 60° C. for 1.5 h
- customPurification via MDAP
Sources & evidence
- ORD record
- ord-db52d03d7c7e49669687b2abc67697dc
- Source dataset
- uspto-grants-2015_11
- Patent number
- US09174968B2
Reaction notes
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