5-BROMO-6-METHOXYPYRIDIN-2-AMINE

A mixture of sodium metal (1.1 g, 47.80 mmol) in MeOH (45 mL) under an argon atmosphere was stirred at -20 Synthesis of 5-bromo-6-methoxypyridin-2-amine To a solution of 6-methoxypyridin-2-amine (10 g, 81 mmol) in acetonitrile (150 mL) was added N-bromosuccinimide (7.17 g, 40.3 mmol). The reaction mixture was stirred at rt for 90 mm. Additional N-bromosuccinimide (7.17 g, 40.3 mmol) in acetonitrile (35 mL) was added, and the reaction mixture was stirred at RT for another 90mm. The reaction mixture was diluted with water (250 mL) and extracted with EtOAc (2x 250 mL). Combined organic extracts were washed with water and brine, dried overNa2SO4 and concentrated. The cmde product was purified by flash chromatography(eluting with 10-15percent EtOAc in hexane) to give 5-bromo-6-methoxypyridin-2-amine(12.1 g, 74percent yield) as an off-white solid. MS(ESI) m/z: 205.3 (M+H) ‘H NMR (300MHz, chloroform-d) ö ppm 7.49 (d, J=8.0 Hz, 1 H), 5.99 (d, J8.0 Hz, 1 H), 4.31 (br. s., 2H), 3.91 (s, 3 H).A 5 mL microwave vial containing a Teflon stirred bar was charged with 5-bromo-6- methoxypyridin-2-amine (90 mg, 0.44 mmol, leq.), 2, 3-dichloro phenylboronic acid (97.2 mg, 0.51 mmol, 1.15 eq.), Na2C03 (140 mg, 1.32 mmol, 3 eq.) followed by the addition of a mixture of Toluene/EtOH/hhO: 3.2/0.5/0.5 (O. lmmol/mL). The vessel was evacuated and backfilled with nitrogen (this process was repeated a total of 3 times) and Pd(PPh )4 (25.6 mg, 0.022 mmol, 0.05 eq.) was introduced. The reaction mixture was then capped properly and placed in a preheated oil bath at l20C until complete conversion of the starting material (usually 3h). The reaction mixture was then concentrated under vacuum and the crude product was purified by chromatography on silica gel using EtOAc/heptane: 1/1 to afford the expected product 7a as a solid (70 mg, 59%)XH-NMR (400 MHz, CDCI3): d 7.39 (dd, J= 6.9 Hz, 2.8 Hz, 1H), 7.25 (d, J= 7.8 Hz, 1H), 7.18 (m, 2H), 6.13 (d, J= 7.8 Hz, 1H), 4.28 (bs, 2H), 3.83 (s, 3H).13C-NMR (101 MHz, CDCI3) d : 159.9, 157.0, 141.4, 138.8, 133.2, 132.8, 130.2, 129.2, 126.8, 111.2, 99.4, 53.6.A 20 mL microwave vial containing a Teflon stirred bar was charged with 5, 6 dibromo pyridine-2 amine (300 mg, 1.12 mmol, 1 eq.), sodium methoxide (167.3 mg, 3.1 mmol, 2.6 eq.), and MeOH (4 mL). The vial was then capped properly and placed in a preheated oil bath at l20C until complete conversion of the starting material was detected (usually 24 hours). The reaction mixture was then concentrated under vacuum and the crude product was purified by chromatography on silica gel using EtO Ac/heptane : 1/1 to afford the expected product as an yellow oil (186 mg, 77%).H-NMR (400 MHz, CDCI3): d 7.49 (d, J= 8.0 Hz, 1H), 5.99 (d, J= 8.0 Hz, 1H), 4.31 (bs, 2H), 3.91 (s, 3H).General procedure: To a solution of To a solution of 5-bromo-6- methoxypyridin-2-amine (4.50 g, 22.16 mmol) in methanol (50 mL) was added Pd(dppf)Ci2.CH2Ci2 (950 mg, 1.16 mmol) under nitrogen atmosphere. The reaction tank was vacuumed and flushed with CO. Then the reaction mixture was stirred for 16 h at 120 C under 20 atm CO atmosphere. When the reaction was done, the reaction mixture was concentrated under reduced pressure and the residue was purified by flash chromatography eluting with EtOAc in hexane (0 % to 100 % gradient) to yield methyl 6-amino-2-methoxypyridine-3-carboxylate as an yellow solid (2.07 g, 51 %). MS: m/z = 182.9 [M+H]+.To a solution of

Molecular Weight:203.04
XLogP3:1.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:201.97418
Monoisotopic Mass:201.97418
Topological Polar Surface Area:48.1
Heavy Atom Count:10
Complexity:112
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes