Hydrochloric Acid → N-{3-Bromo-5-[(methylsulfanyl)methyl]phenyl}-5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidin-2-amine

HRID 2277755Notes

Reaction equation

Cl.O1CCOCC1.Cl[C:9]1[N:14]=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=2[O:22][CH3:23])[C:12]([F:24])=[CH:11][N:10]=1.[Br:25][C:26]1[CH:27]=[C:28]([CH:30]=[C:31]([CH2:33][S:34][CH3:35])[CH:32]=1)[NH2:29]>C(O)CCC.C(OCC)(=O)C>[Br:25][C:26]1[CH:27]=[C:28]([NH:29][C:9]2[N:14]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=3[O:22][CH3:23])[C:12]([F:24])=[CH:11][N:10]=2)[CH:30]=[C:31]([CH2:33][S:34][CH3:35])[CH:32]=1

Participants

Conditions

Temperature: 140 °C

Procedure

A 4N solution of hydrogen chloride in dioxane (0.54 mL; 2.15 mmol) was added to a stirred solution of 2-chloro-5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidine (553 mg; 2.15 mmol) and 3-bromo-5-[(methylsulfanyl)methyl]aniline (500 mg; 2.15 mmol) in 1-butanol (4.8 mL). The batch was stirred at 140° C. for 8 hours. After cooling the batch was diluted with ethyl acetate and washed with sodium bicarbonate and saturated aqueous sodium chloride solution. The organic phase was filtered using a Whatman filter and concentrated. The residue was purified by chromatography (hexane/ethyl acetate 4:1) to give the desired product (450 mg; 0.99 mmol).

Workup

temperatureAfter cooling the batch
washwashed with sodium bicarbonate and saturated aqueous sodium chloride solution
filtrationThe organic phase was filtered
filtrationfilter
concentrationconcentrated
customThe residue was purified by chromatography (hexane/ethyl acetate 4:1)

Sources & evidence

ORD record: ord-3d69db03f8594a7e898c8ea8dfda43ef
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133171B2

Reaction notes

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