2-Methylthio-4-pyrimidinol

White Solid

2-methylthiouracil is an aryl sulfide.

Preparation of 5-bromo-2-methylthio-4-pyrimidinone: Take 142 g of 2-methylthio-4-pyrimidinone, dissolve in 500 ml of methylene chloride, add NBS 190 g, reflux for 6 hours, After the reaction is completed, cool to room temperature, filter, wash the filtrate, organicThe phase was dried and recrystallized on an ice bath to give 190 g of a pale yellow solid in a yield of 87percent.(EX-6B) A solution of EX-6A (74.0 g, 520.5 mmol) in glacial acetic acid (2275 mL) was cooled to 0° C. with an ice bath and treated with Br2. The reaction mixture was allowed to warm to room temperature, and to stir for 16 h. A yellow precipitate formed which was filtered and washed with ether three times. 97.2 g of EX-6B was isolated in 62percent yield.To a solution containing 2.0 g (14 mmol) of 2- (methylthio) pyrimidin-4(3H)-one in 10 ml of acetic acid under a nitrogen atmosphere was added 1.04 ml (14 mmol) of bromine in 2 ml acetic acid. The reaction was allowed to stir at room temperature for 30 min. The precipitated product was filtered, washed with acetic acid and suspended in hot acetic acid- To this suspention was added 0.2 ml bromine in 1ml acetic acid. The product was collected, washed with acetic acid and recrystallized from ethanol to yield 1.4 g (45 percent) of product. 1H NMR (CD30D) 5: 2. 61 (s, 3H) , 8.29 (s, 1H).Synthetic routeSynthetic routeTo a mixture of HOAc (500 mL) and Ac2O (10 mL) was added compound 2- (methylthio)pyrimidin-4(3H)-one (40 g, 0.28 mol). The resulting mixture was heated at 80 °C for 30 min to remove any moisture. Then NCS (49 g, 0.37 mol) was added at 50-60 °C. The resulting mixture was stirred at 50-60 °C for 24 h. The mixture was then cooled to room temperature and was poured into ice-water (500 mL). The solid formed was collected and was treated with MeOH (100 mL) at reflux. Then the solid was filtered and dried on vacuum to give title compound (24 g, 48percent) as a white solid.To a solution of 2-methylthio-4-ketopyrimidine (14, 10.27 g, 70.4 mmol) in DCM (20 mL) and DMF (10 mL)mixed solution, thionyl chloride (3.05 mL, 42.2 mmol) solution was slowly added dropwise while heating. After addition, the reaction mixture was stirred at 40 °C for 3 h. After quenching with saturated NaHCO3, the solution was adjusted to a neutral pH and the solution was extracted three times with DCM. The organic phases were washed with saturated NaHCO3 solution and saturated NaCl solution and dried over anhydrous Na2SO4. After filtering to remove the anhydrous Na2SO4, the solution was distilled at40 °C to remove solvents under atmospheric pressure to give product 15 as a yellow oil (10.19 g, 87.6percent). 1H NMR(300 MHz, CDCl3) delta 8.38 (d, J = 5.2 Hz, 1H), 6.99 (d, J = 5.2 Hz, 1H), 2.53 (s, 3H); 13C NMR (75 MHz, CDCl3) delta174.0, 161.0, 158.0, 116.4, 14.3; HRMS ([M + H]+): m/zcalcd for C5H5ClN2S: 160.9940; found: 160.99335.

A competitive inhibitor of Nitric Oxide Synthase (NOS).

Molecular Weight:142.18
XLogP3:0.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:142.02008399
Monoisotopic Mass:142.02008399
Topological Polar Surface Area:66.8
Heavy Atom Count:9
Complexity:185
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes