Methyl iodide → 1-(2-Chloro-6-methyl-pyridine-4-carbonyl)-3-(3,4-difluoro-phenyl)-2-methyl-isothiourea

HRID 2092215Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[C:16]([F:21])[CH:15]=2)=[S:12])=[O:9])[CH:5]=[C:4]([CH3:22])[N:3]=1.[H-].[Na+].[CH3:25]I>C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([NH:10][C:11](=[N:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[C:16]([F:21])[CH:15]=2)[S:12][CH3:25])=[O:9])[CH:5]=[C:4]([CH3:22])[N:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A mixture of intermediate D1 (38 g; 111.4 mmol) in THF (400 ml) was cooled to 0° C. and NaH (60% pure) (6.7 g; 167 mmol) was carefully added. The reaction mixture was stirred for 15 minutes and then CH3I (14.2 g; 100 mmol) was added. The mixture was then warmed to room temperature and stirred for 2 hours. The reaction was quenched by the addition of water and then the mixture was extracted by CH2Cl2 (3×100 ml). The combined organic solvent was washed with brine, dried over MgSO4, filtered and the solvent was evaporated in vacuo. The residue was purified by silica column chromatography (gradient: Heptane/EtOAc from 80/20 to 50/50). Yield: 22.2 g of intermediate D2.

Workup

temperatureThe mixture was then warmed to room temperature
stirringstirred for 2 hours
customThe reaction was quenched by the addition of water
extractionthe mixture was extracted by CH2Cl2 (3×100 ml)
washThe combined organic solvent was washed with brine
dry with materialdried over MgSO4
filtrationfiltered
customthe solvent was evaporated in vacuo
customThe residue was purified by silica column chromatography (gradient: Heptane/EtOAc from 80/20 to 50/50)

Sources & evidence

ORD record: ord-6206051bb87140c9a90a674b9b3acb97
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08440701B2

Reaction notes

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