Thionyl Chloride → 5-(chloromethyl)-N-(4-(difluoromethoxy)phenyl)-4-methoxypyrimidin-2-amine hydrochloride

HRID 77465Notes

Reaction equation

S(Cl)([Cl:3])=O.[F:5][CH:6]([F:25])[O:7][C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15]2[N:20]=[C:19]([O:21][CH3:22])[C:18]([CH2:23]O)=[CH:17][N:16]=2)=[CH:10][CH:9]=1>C(Cl)Cl>[ClH:3].[Cl:3][CH2:23][C:18]1[C:19]([O:21][CH3:22])=[N:20][C:15]([NH:14][C:11]2[CH:12]=[CH:13][C:8]([O:7][CH:6]([F:25])[F:5])=[CH:9][CH:10]=2)=[N:16][CH:17]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Thionyl chloride (0.295 mL, 4.04 mmol) was added to a suspension of ((2-((4-(difluoromethoxy)phenyl)amino)-4-methoxypyrimidin-5-yl)methanol (0.3 g, 1.009 mmol) in DCM (10 mL) cooled to 0° C. The mixture was stirred for 18 h while warming to room temperature. The reaction mixture was concentrated and dried under vacuum to give 5-(chloromethyl)-N-(4-(difluoromethoxy)phenyl)-4-methoxypyrimidin-2-amine hydrochloride as a beige solid (0.35 g, 97%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.98 (s, 1H), 8.34 (s, 1H), 7.87-7.72 (m, 2H), 7.42-6.86 (m, 3H), 4.67 (s, 2H), 4.02 (s, 3H).

Workup

temperaturewhile warming to room temperature
concentrationThe reaction mixture was concentrated
customdried under vacuum

Sources & evidence

ORD record: ord-500c68c734dc453c8964554184aa6180
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08841301B2

Reaction notes

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