5-Bromo-6-methoxy-3-pyridinecarboxylic acid

(5-bromopyridin-2-yl) ((2S) -2- (4-chlorophenyl) piperazin- 1 - yl) methanone hydrochloride(200 mg), 5-Bromo-6-methoxynicotinic acid (130 mg), HATU (250 mg), Triethylamine (0.15 ml) and DMF (3 ml)Was stirred at room temperature for 2 hours.The mixture was extracted with ethyl acetate and water. The obtained organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) and silica gel column chromatography (NH, hexane / ethyl acetate) to give the title compound (223 mg).Step 2: 1 -{[5-Bromo-6-methoxy-pyridine-3-carbonyl]-amino}-cycloheptanecarboxylic acid methyl esterThe compound of step 1 (1 .85 g, 7.97 mmol) was dissolved in thionyl chloride (6 ml) and stirred for 30 min at 60 C. The volatiles were evaporated in vacuo, the residue was dissolved in DCM and added to a stirred mixture of 1 -amino- cycloheptanecarboxylic acid methyl ester hydrochloride, EA and saturated sodium hydrogencarbonate solution with ice cooling. The mixture was stirred at room temperature overnight, the phases were separated and the aqueous phase was extracted with EA. The combined organic phases were dried over sodium sulfate and evaporated to dryness to yield the title compound (2.80 g).1H-NMR: delta = 8.62 (d, 1 H); 8.52 (s, 1 H); 8.48 (d, 1 H); 3.99 (s, 3H); 3.57 (s, 3H); 2.15- 2.01 (m, 4H); 1 .65-1 .43 (m, 8H)Step 1 : 5-Bromo-6-methoxy-nicotinic acid5-Bromo-6-methoxy-nicotinic acid methyl ester (W. J. Thompson et al., J. Org. Chem 49 (1984), 5237-5243; 2.00 g, 8.13 mmol) was dissolved in dioxane (40 ml), lithium hydroxide (40 ml of a 1 M solution in water) was added and subsequently sufficient methanol to achieve complete dissolution. The mixture was stirred at 60 C for 2 h. The methanol was evaporated in vacuo and the remaining mixture was acidified with 2 N hydrochloric acid and extracted with EA. The combined extracts were dried over sodium sulfate, filtered and evaporated to dryness to yield the title compound.1H-NMR: delta = 13.3 (s, 1 H); 8.68 (d, 1 H); 8.35 (d, 1 H); 4.01 (s, 3H)

Molecular Weight:232.03
XLogP3:1.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:230.95311
Monoisotopic Mass:230.95311
Topological Polar Surface Area:59.4
Heavy Atom Count:12
Complexity:176
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes