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

HRID 2277749Notes

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

Participants

Conditions

Temperature: 140 °C

Procedure

A 4N solution of hydrogen chloride in dioxane (0.61 mL; 2.45 mmol) was added to a stirred solution of 2-chloro-5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidine (630 mg; 2.45 mmol) and 3-[(methyl-sulfanyl)methyl]aniline (564 mg; 3.68 mmol) in 1-butanol (5.4 mL). The batch was stirred at 140° C. for 16 hours. After cooling the batch was diluted with ethyl acetate and washed with aqueous sodium bicarbonate solution 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 2:1) to give the desired product (662 mg; 1.77 mmol).

Workup

temperatureAfter cooling the batch
washwashed with aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution
filtrationThe organic phase was filtered
filtrationfilter
concentrationconcentrated
customThe residue was purified by chromatography (hexane/ethyl acetate 2:1)

Sources & evidence

ORD record: ord-57844259a38f41d4ad8be1906f9a8075
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133171B2

Reaction notes

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