Hydrogen Bromide → 5-(2,5-difluoro-4-hydroxyphenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one

HRID 1676379Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([O:8]C)[C:5]([F:10])=[CH:4][C:3]=1[C:11]1[C:12](=[O:25])[N:13]([CH3:24])[C:14]([NH:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[N:15][CH:16]=1.Br.[OH-].[Na+]>CC(O)=O.O>[F:1][C:2]1[CH:7]=[C:6]([OH:8])[C:5]([F:10])=[CH:4][C:3]=1[C:11]1[C:12](=[O:25])[N:13]([CH3:24])[C:14]([NH:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[N:15][CH:16]=1

Participants

Conditions

Temperature: 125 °C

Procedure

5-(2,5-difluoro-4-methoxyphenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one (0.066 g, 0.192 mmol) was dissolved in AcOH (2 mL) and HBr (1.087 ml, 9.612 mmol; 48 wt % in H2O) was added. The mixture was stirred at 125° C. for 3 days. The reaction mixture was cooled to room temperature and then diluted with H2O. The pH of the reaction mixture was adjusted to a pH of about 5 with 6M aqueous NaOH, which resulted in the formation of an off-white precipitate that was filtered and washed with H2O. The solid was dried directly in the fritted funnel under vacuum overnight and then dissolved through with MeOH/THF and concentrated. The product was obtained (58 mg; 92%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 10.33 (br s, 1H), 8.91 (br s, 1H), 7.70 (s, 1H), 7.55-7.48 (m, 2H), 7.36 (t, 2H), 7.23 (m, 1H), 7.14 (m, 1H), 6.77 (m, 1H), 3.53 (s, 3H). LRMS (ESI pos) m/e 330 (M+1).

Workup

temperatureThe reaction mixture was cooled to room temperature
customresulted in the formation of an off-white precipitate that
filtrationwas filtered
washwashed with H2O
customThe solid was dried directly in the fritted funnel under vacuum overnight
dissolutiondissolved through with MeOH/THF
concentrationconcentrated
customThe product was obtained (58 mg; 92%) as an off-white solid

Sources & evidence

ORD record: ord-6d707f6d03f94f80ad901c54e0650752
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08003662B2

Reaction notes

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