2-chloro-6-methoxypyridin-4-amine

2-Chloro-6-methoxypyridin-4-amine (41.6.B). A solution of2, 6-dichloropyridin-4-amine 41.6.A (available from Aldrich) (3.10 g, 19.0 mmol) in 20percent NaOMe/MeOH (15 mL) was refluxed for 72 hr. The reaction mixture was diluted with HIntermediate 35 : 4-Chloro-6-methoxy-pyridine-2-carboxylic acid 35.1 : 2-Chloro-6-methoxy-pyridin-4-ylamine To a solution of 1.84 g (44.0 mmol) sodium in 40 mL MeOH was added 6.72 g (40.0 mmol) 2, 6- dichloro-pyridin-4-ylamine. The reaction mixture was stirred at 150 °C for 30 min under microwave irradiation. The solvent was evaporated and ice water was added. The precipitate was filtered off, washed with water and dried. yield: 5.00 g (79 percent); ESI-MS: m/z = 159 (M+H)35.1: 2-Chloro-6-methoxy-pyridin-4-ylamine To a solution of 2, 6-dichloropyridin-4-amine (2.80 g, 17.2 mmol) in NMP (25 mL) was addedCH3ONa (3.72 g, 68.8 mmol). The mixture was stirred at 140 °C overnight. The reactionmixture was cooled to rt and poured into water (150 mL). The mixture was extracted withEtOAc (50 mL x 3). The combined organic layers were washed with water (50 mL) and brine (50 mL), dried over Na2SO4 and concentrated. The residue was purified by columnchromatography (PE: EtOAc = 10: 1) to give the title compound (2.0 g, yield 74percent) as a whitesolid.D489 1H NMR (300 MHz, CDCI3): ö 6.23 (s, 1H), 5.83 (s, 1H), 4.16 (brs, 2H), 3.86 (s, 3H).A pressure vessel was charged with 4-Amino-2, 6-dichloropyridine (Combi-Blocks, 1.0 g, 6.1 mmol, 1 eq) and a stir bar. The system was purged with Ar. NaOMe (0.5 N in MeOH, 20 mL, 10 mmol, 1.63 eq) was added. The vessel was closed, and the reaction was heated to 130 °C. After 4 days only partial conversion was observed. The temperature was increased to 160 °C. After 20 h the reaction was cooled to room temperature, and the volatiles were removed via rotary evaporation. The residue was partitioned between EtOAc/water, and the layers were separated. The organic layer was washed with water (x2), brine (xl), and dried over Na2SO4. The solids were filtered off, and the volatiles were removed via rotary evaporation. The residue was dissolved in DCM. Silica gel (5 g) was added, and the volatiles were removed via rotary evaporation. Purification via flash chromatography eluting with 0-25percent EtOAc in hexanes yielded 0.843 g (5.3 mmol, 87percent yield) of 187 as an off-white solid.

Molecular Weight:158.58
XLogP3:1.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:158.0246905
Monoisotopic Mass:158.0246905
Topological Polar Surface Area:48.1
Heavy Atom Count:10
Complexity:112
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes