4-Chloro-5-methoxypyrimidine

General procedure: PdClA suspension of 1.9 g (0.015 mol) of 5-methoxy-3H-pyrimidin-4-one (Example P2) in 4.2 ml (0.046 mol) of phosphorus oxychloride and 5.0 mi (0.031 mol) of N, N-diethylaniline is heated at 115°C for 3 hours. The dark, homogeneous mixture obtained is hydrolyse by adding crushed ice, the temperature being kept below 30°C. Extraction with diethyl ether, drying of the combined organic ethereal phases over sodium sulfate, and purification on a silica gel column (eluant : ethyl acetate/n-hexane 1/9) yields the desired target compound in a yield of 1.3 g (58 percent of theory). Further purification by means of sublimation at 80-85°C/15 Torr yields the desired title compound, having a melting point of 63-64°C. oh NMR (300 MHz, Ceci3) : 8.635 ppm (s, 1H) ; 8.321 ppm (s, 1H) ; 4.025 ppm (s, 3H).A suspension of 5-methoxypyrimidin-4-ol (1-88) (57 g, 0.452 mol) in POCI3 (540 mL) was heated at reflux for 6 hr. TLC (CH2CI2/MeOH =10:1 ) showed the reaction was complete. Most of the POCI3 was removed under reduced pressure, and the residue was poured into ice-water (2 L), basified with K2C03 (250 g) to pH ~ 7. The mixture was then extracted with EtOAc BME (3:1 , 4 x 250 mL). The organic layers were combined, washed with brine (100 mL) and dried over Na2S04, filtered and concentrated in vacuo to give 4-chloro-5-methoxypyrimidine (I-89) (3S g, 58percent) as a yellow solid. 1H NMR (400 MHz, DMSO-c/6) 8 ppm 8.63 (s, 1 H), 8.32 (s, 1 H), 4.02 (s, 3 H).The compound A suspension of 5-methoxypyrimidin-4-ol (1-88) (57 g, 0.452 mol) in POCI3 (540 mL) was heated at reflux for 6 hr. TLC (CH2CI2/MeOH =10:1 ) showed the reaction was complete. Most of the POCI3 was removed under reduced pressure, and the residue was poured into ice-water (2 L), basified with K2C03 (250 g) to pH ~ 7. The mixture was then extracted with EtOAc BME (3:1 , 4 x 250 mL). The organic layers were combined, washed with brine (100 mL) and dried over Na2S04, filtered and concentrated in vacuo to give To a stirred solution of (rac)-tert-butyl 4-[1 -(2-{[6-(4 4, 5, 5-tetramethyl- 1, 3 , 2-dioxaborolan-2-yl)-1 H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazine-1 -carboxylate (1.60 g, 2.92 mmol)and To a stirred solution of (rac)-tert-butyl 4-[1-(2-{[6-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl)-I H-benzimidazol-2-yl]amino}pyridin-4-yl)ethyl]piperazine-1 -carboxylate (1.00 g, 1.82 mmol)and 4-chloro-6-methoxypyrirnidine (422 mg, 2.92 mmol) in dioxane (9 mL) and water (1.8 mL)was added sodium carbonate (773 mg, 7.29 mmol) and Pd(dppf)C12 . CHCl (223 mg, 273ljmol). The mixture was heated to reflux for 24 h. Further 4-chloro-6-methoxypyrimidine (130mg) was added and the mixture was heated to reflux for 24 h. Dichioromethane was added, the mixture was dried (magnesium sulfate), filtered and the solvent was removed in vacuum. Silicagel chromatography gave 0.43 g (45 % yield) of the title compound.General procedure: PdCl2(dppf), PdCl2(tbpf) and (A.caPhos)PdCl2. A mixture of the halogenated heterocycle (0.66 mmol) in anhydrous THF (13.2 mL) was degassed by bubbling argon for few minutes. Then, PdCl2(dppf) (27.0 mg, 0.033 mmol, 5.0 mol%), TMEDA (0.130 g, 1.12 mmol, 1.7 equiv) and finally NaBH4 (42.4 mg, 1.12 mmol, 1.7 equiv) were introduced in sequence. The mixture was stirred at room temperature under argon for the proper time and then worked up as described above.To a solution of

Molecular Weight:144.56
XLogP3:1.1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:144.0090405
Monoisotopic Mass:144.0090405
Topological Polar Surface Area:35
Heavy Atom Count:9
Complexity:91
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes