Acetonitrile → 6-Amino-2-(4-chlorophenyl)pyrimidine-4-carboxylic acid

HRID 2282942Notes

Reaction equation

P(Cl)(Cl)(Cl)=O.[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[NH:14][C:15](=O)[CH:16]=[C:17]([C:19]([OH:21])=[O:20])[N:18]=2)=[CH:9][CH:8]=1.C(#[N:25])C>O>[NH2:25][C:15]1[N:14]=[C:13]([C:10]2[CH:11]=[CH:12][C:7]([Cl:6])=[CH:8][CH:9]=2)[N:18]=[C:17]([C:19]([OH:21])=[O:20])[CH:16]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To phosphorus oxychloride (180 mL) was added 2-(4-chlorophenyl)-1,6-dihydro-6-oxo-4-pyrimidinecarboxylic acid (i.e. the product of Step A) (81.81 g, 326 mmol). The mixture was heated to 90° C. for 2.5 h. After cooling to room temperature the reaction mixture was slowly added to 1:2 acetonitrile:water (1.5 L) while keeping the temperature between 35 and 45° C. After the reaction mixture was stirred at room temperature for 30 minutes the resulting solid was isolated by filtration and washed with water. The solid was then combined with aqueous ammonia (5%, 2.1 L) and heated to 80° C. for 18 h. After 2 days at room temperature the solid was isolated by filtration and washed with water. A second crop was obtained by cooling the filtrate and refiltering. The combined solids were dried to afford the title compound (58.8 g).

Workup

temperatureAfter cooling to room temperature the reaction mixture
customthe temperature between 35 and 45° C
customwas isolated by filtration
washwashed with water
temperatureheated to 80° C. for 18 h
customAfter 2 days at room temperature the solid was isolated by filtration
washwashed with water
customA second crop was obtained
temperatureby cooling the filtrate and refiltering
customThe combined solids were dried

Sources & evidence

ORD record: ord-3eefd357afef4416b790c105dabe9d0e
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09144240B2

Reaction notes

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