Potassium Carbonate → 6-(4-fluorobenzylthio)-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrimidin-4(3H)-one

HRID 2059874Notes

Reaction equation

Cl[C:2]1[N:7]=[CH:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]([OH:19])([CH3:18])[CH3:17])=[C:10]([O:20][CH3:21])[CH:9]=2)[C:4](=[O:22])[CH:3]=1.[F:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30][SH:31])=[CH:26][CH:25]=1.C(=O)([O-])[O-].[K+].[K+]>C1COCC1.C(Cl)Cl>[F:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30][S:31][C:2]2[N:7]=[CH:6][N:5]([C:8]3[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]([OH:19])([CH3:18])[CH3:17])=[C:10]([O:20][CH3:21])[CH:9]=3)[C:4](=[O:22])[CH:3]=2)=[CH:26][CH:25]=1

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of 6-chloro-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrimidin-4(3H)-one Part A of procedure 11 (20 mg, 0.06 mmol), (4-fluorophenyl)methanethiol (26 mg, 0.18 mmol), and potassium carbonate (25.5 mg, 0.185 mmol) in THF (0.5 mL) was stirred at 70° C. overnight. The reaction was diluted with CH2Cl2, filtered, and concentrated. The crude product was purified using HPLC (Phen Luna Axia C18 5μ 10:90:0.1 to 90:10:0.1 MeOH—H2O-TFA) to afford the desired product 6-(4-fluorobenzylthio)-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrimidin-4(3H)-one H-3 (17.25 mg, 0.038 mmol, 61.8% yield) as off-white solid. LC/MS 431 (M+H)+, tR 0.91 min (method 5). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.14 (1H, s), 7.35-7.45 (2H, m), 6.95-7.09 (3H, m), 6.80-6.90 (2H, m), 6.49 (1H, s), 4.28 (2H, s), 3.88 (5H, s), 1.39 (6H, s)

Workup

filtrationfiltered
concentrationconcentrated
customThe crude product was purified

Sources & evidence

ORD record: ord-dce22149595c43e58f470e3478878851
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08278316B2

Reaction notes

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