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

HRID 474824Notes

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][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]

Participants

Conditions

Temperature: 60 °C

Procedure

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

Workup

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

Sources & evidence

ORD record: ord-2c8b0243af8c44e2a68bddd6d1ccab52
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637536B2

Reaction notes

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