5-BROMO-4-CHLORO-2-METHYLSULFANYL-PYRIMIDINE

White solid

Step 3, Preparation of 5-bromo-4-chloro-2-methylthiopyrimidine: take 5-bromo-2-methylthio-4-pyrimidinone 110g, dissolve in 400g pyridine, and raise the temperature of the system to 80°.100 g of phosphorus oxychloride was added dropwise. After the addition was completed, the reaction was continued for 5 h. After the reaction was completed, Cool to room temperature, ice bath, adjust the pH to 8-9 with saturated sodium bicarbonate, extract with 500 ml of ethyl acetate, dry over anhydrous magnesium sulfate, filter, The filtrate was decompressed to recover the solvent, and the residue was recrystallized from petroleum ether:ethyl acetate=1:3 to obtain 98 g of light yellow solid powder in a yield of 83percent.Step 3, Preparation of 5-bromo-4-chloro-2-methylthiopyrimidine: take 5-bromo-2-methylthio-4-pyrimidinone 110g, dissolve in 400g pyridine, and raise the temperature of the system to 80°.100 g of phosphorus oxychloride was added dropwise. After the addition was completed, the reaction was continued for 5 h. After the reaction was completed, Cool to room temperature, ice bath, adjust the pH to 8-9 with saturated sodium bicarbonate, extract with 500 ml of ethyl acetate, dry over anhydrous magnesium sulfate, filter, The filtrate was decompressed to recover the solvent, and the residue was recrystallized from petroleum ether:ethyl acetate=1:3 to obtain 98 g of light yellow solid powder in a yield of 83percent.Compound 44. A mixture of compound 42 (1.0 g, 4.22 mmol, 1.5 eq.), compound 43 (1.2 g, 2.82 mmol, 1 eq.), Pd(PPh3)4 (325 mg, 282 mumol, 0.1 eq.), and LiCl (239 mg, 5.63 mmol, 2 eq.) in toluene (10 mL) was degassed and purged with N2 for 3 times. Then the mixture was stirred at 100 C for 8 h under N2. The reaction mixture was cooled down to 25 oC and partitioned between sat. KF (30 mL) and EtOAc (40 mL). The organic phase was separated, washed with brine (20 mL), dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography (PE/EtOAc: 10/1 to 3/1) to afford compound 44 (400 mg, 1.18 mmol, 42% yield). 1H NMR (CDCl3, 400 MHz) delta 8.72 (s, 1H), 4.11 (s, 3H), 3.00 (d, J = 6.7 Hz, 2H), 2.57 (s, 3H), 1.07-0.92 (m, 1H), 0.57-0.46 (m, 2H), 0.32-0.17 (m, 2H).To a solution of 4-chloro-2-(methylthio)-pyrimidine (15, 10.19 g, 63.4 mmol) in MeOH (28 mL) and MeCN (20 mL) mixed solution, NBS (13.55 g, 76.1 mmol) was added (2 × 3.76 g). After the additions, the reaction mixture was stirred at room temperature. After quenching with saturated Na2SO3 solution, the solution was extracted with DCM and saturated NaHCO3 solution three times. The combined organic phases were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by passing the organic extract through a silica gel column using PE/EA(25:1) to give the product 16 as a white solid (11.02 g, 72.5%); m.p. 48.5-50.1 C. 1H NMR (300 MHz, CDCl3) delta8.54 (s, 1H), 2.55 (s, 3H). 13C NMR (75 MHz, CDCl3) delta172.1, 159.5, 114.1, 14.7. HRMS ([M + H]+): m/z calcd forC5H4BrClN2S: 240.9025; found: 240.90203.To a solution of 4-chloro-2-(methylthio)-pyrimidine (21, 9.90 g, 61.6 mmol) in MeOH (28 mL) and MeCN (20 mL)mixed solution, NBS (13.16 g, 73.9 mmol) was added(2 × 6.58 g). After the additions, the reaction mixture wasstirred at room temperature. After quenching with saturatedNa2SO3solution, the solution was extracted with DCMand saturated NaHCO3solution three times. The combinedorganic phases were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by passingthe organic extract through a silica gel column using PE/EA(25:1) to give the product 22 (Elliott 1981). White solid;yield 73%; m.p. 48.5-50.1 C; 1H NMR (300 MHz, CDCl3)delta 8.54 (s, 1H), 2.55 (s, 3H); 13C NMR (75 MHz, CDCl3)delta172.1, 159.5, 114.1, 14.7; HRMS ([M + H]+): m/z calcd for[(C5H4BrClN2S) + H]+: 240.90254, found: 240.90203.To a stirred solution of A solution of ethyl 2-(diphenylmethyleneamino)acetate (2.2) (18.4 g, 69mmol) in DMSO (50 ml) was added dropwise to a suspension of NaH (60%) (5.Og, 125.5mmol) in anhydrous DMSO (70 mL) at 0 C. The reaction mixture turned orangeimmediately. 2 mm later,

Molecular Weight:239.52
XLogP3:2.7
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:237.89671
Monoisotopic Mass:237.89671
Topological Polar Surface Area:51.1
Heavy Atom Count:10
Complexity:116
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes