Hydrochloric Acid → 5-Chloro-6-fluoro-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

HRID 2090555Notes

Reaction equation

[NH2:1][C:2]1(C#N)[CH2:7][C:6]([Cl:8])=[C:5]([F:9])[C:4](=[O:10])[N:3]1[CH3:11].Cl>C(O)=O>[Cl:8][C:6]1[C:7]2[C:4](=[O:10])[NH:3][CH:2]=[N:1][C:2]=2[N:3]([CH3:11])[C:4](=[O:10])[C:5]=1[F:9]

Participants

Conditions

Temperature: 70 °C

Procedure

Combine 2-amino-5-fluoro-4-chloro-1-methyl-6-oxo-1,6-dihydropyridine-carbonitrile (33.0 g, 0.164 mol) and 99% formic acid (264 mL, 8 volumes) in a dried vessel. Heat to 70° C. When a solution is formed, add concentrated aqueous hydrochloric acid (165 mL, 5 volumes). After 20 hours, add another portion of concentrated aqueous hydrochloric acid (35 mL) and heated at 70° C. for another 4 h. Then cool the reaction mixture to the ambient temperature and add ice-water (350 mL, 10 volumes). Cool in an ice bath to give a solid. After 30 minutes, collect the solid by filtration, rinse with water (2×30 mL), and dry in vacuo to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ12.96 (s, 1H), 8.35 (s, 1H). 3.61 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ157.7 (d, J=4.4 Hz), 154.6 (d, J=26.4 Hz), 151.2 (d, J=2.2 Hz), 149.9, 146.4 (d, J=242 Hz), 125.0 (d, J=16.9 Hz), 99.94, 29.8; 19F NMR (376 MHz, DMSO-d6) δ−133.8; MS (M+H)+m/z calcd 230.0. found 230.0.

Workup

customWhen a solution is formed
temperatureheated at 70° C. for another 4 h
temperatureThen cool the reaction mixture to the ambient temperature
temperatureCool in an ice bath
customto give a solid
waitAfter 30 minutes
customcollect the solid
filtrationby filtration
washrinse with water (2×30 mL)
customdry in vacuo

Sources & evidence

ORD record: ord-b8ae269099dd4aaf97b150900dd5da32
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08436200B2

Reaction notes

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