Methyl-5-bromo-2 pyrimidine carboxylate

To a solution of 5-bromopyrimidine-2-carboxylic acid (3.22 g, 15.9 mmol) in MeOH (50 mL) at room temperature was added acetyl chloride (4.0 mL, 56.3 mmol). The reaction mixture was heated to reflux for 15 min, cooled to room temperature and concentrated under reduced pressure. The reaction mixture was diluted with saturated NaHCC>3 (30 mL) and EtOAc, and transferred to a separatory funnel. The aqueous phase was extracted with EtOAc (4 x) and the combined organic extracts were washed with brine (1 x), dried over MgS0To a solution of 5-bromopyrimidine-2-carboxylic acid (3.22 g, 15.9 mmol) in MeOH (50 mL) at room temperature was added acetyl chloride (4.0 mL, 56.3 mmol). The reaction mixture was heated to reflux for 15 min, cooled to room temperature and concentrated under reduced pressure. The reaction mixture was diluted with saturated NaHCOPreparation 65 5-Bromo-pyrimidine-2-carboxylic acid methyl ester Fuming hydrochloric acid was passed through an ice-cooled SOTUTIBN OF THE- product of preparation 64 (5. 5g. 27mmol) in methanol (50mL) until saturated The reaction mixture was warmed to room temperature and was stirred for 18- hours. The solvent was then evaporated under reduced pressure and. the- residue was dissolved in dichloromethane, washed with water and sodium HYDROGEN CARBONATE SOLUTION, DRIED-OVER MAGNESIUM SULFATE. AND CONCENTRATED IN-: O AFFORD THETITLE compound as yellow. solid in 57percent yield, 3.5g. HNMR (CDC) 3. 400MHZ) .sect. : 4, 65 (s, 3H), 9. 00 (s, 2H). MS AP +To a solution of 5-bromopyrimidine-2-carbonitrile (3.0 g, 16 mmol) in MeOH (20 mL) was added concentrated HCl (19 mL). To a solution of 5-bromopyrimidine-2-carboxylic acid (500 mg, 2.47 mmol) in DCM (5.0 mL), in a two-necked flask equipped with a bubbler, was added oxalyl chloride (0.23 mL, 2.72 mmol) and two drops of DMF at room temperature. After stirring for 1.5 h, the solvent was removed in vacuo. The acyl chloride was dissolved in CH2C12 (5.0 mL) and added MeOH (0.20 mL, 4.93 mmol) at 0 °C. After stirring for 2 h, the reaction mixture was quenched by adding saturated NaHCC solution. The crude products were extracted with CH2C12 (x3), and the combined organic extracts were washed with brine, dried (MgS04), and concentrated in vacuo. The residue was purified by flash column chromatography (hexane/EtOAc = 3/1 to 2/1) to afford desired methyl 5-bromopyrimidine-2-carboxylate (294 mg, 90percent) as a white solid. NMR (300 MHz, CDCh) δ 9.01 (s, 2H), 4.10 (s, 3H).To a mixture of 4 To a 250 mL round-bottom flask was added (lR, 3S, 5S)-8-azabicyclo[3.2.1]octan-3 cyclopropyl-3-(2, 6-dichlorophenyl)-l, 2-oxazole-4-carboxylate lj (500 mg, 1.23 mmol equiv.), To a 25 mL round-bottom flask was added (1S, 4S, 5R)-5-[[4-cyclopropyl-l-(2, 6- dichlorophenyl)-1H-pyrazol-5-yl]methoxy]-2-azabicyclo[2.2.1]heptane li (156 mg, 0.41 mmol, 1.00 equiv.), Ruphos precatalyst (66 mg, 0.20 equiv.), Ruphos (37 mg, 0.20 equiv.), Cs2CO3 (390 mg, 1.20 mmol, 3.00 equiv.), Under the protection of N2, PdCl2(dppf) (0.337 g, 0.461 mmol) was added to an anhydrous 1, 4-dioxane (200 mL) solution of To a mixture of

Molecular Weight:217.02
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:215.95344
Monoisotopic Mass:215.95344
Topological Polar Surface Area:52.1
Heavy Atom Count:11
Complexity:146
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes