2-Hydroxynicotinaldehyde

2-Chloronicotinaldehyde (0.283 g, 2.00 mmol) was suspended 3M aqueous HCl (2 mL). 4 drops of 3percent HGeneral procedure: To a stirred solution of aldehyde 1 (4.711 mmol), 5-amino tetrazole 2 (4.711 mmol) and ethyl acetoacetate/ tert-Butyl acetoacetate 3/5 (4.711 mmol) in polyethylene glycol (PEG)-400 (5 mL) and the mixture was heated at 110 C for 30 min under microwave irradiation. The progress of the reaction was monitored by TLC. After completion of reaction, cooled to RT, diluted with cold water (20 mL), solid precipitated was filtered, washed with diethyl ether (20 mL), and dried under vacuum.General procedure: To a stirred solution of aldehyde 1 (4.711 mmol), 5-amino tetrazole 2 (4.711 mmol) and ethyl acetoacetate/ tert-Butyl acetoacetate 3/5 (4.711 mmol) in polyethylene glycol (PEG)-400 (5 mL) and the mixture was heated at 110 C for 30 min under microwave irradiation. The progress of the reaction was monitored by TLC. After completion of reaction, cooled to RT, diluted with cold water (20 mL), solid precipitated was filtered, washed with diethyl ether (20 mL), and dried under vacuum.General procedure: To a solution of 2-nitrofluorene (211 mg, 1.0 mmol) and o-anisaldehyde(272 mg, 2.0 mmol) in 5mL of methanol was added KFAl2O3(160 mg, 1.0 mmol). The reaction mixture was stirred at 65 Cfor 16 h, and then evaporated in vacuo. The residue was purified bysilica gel column chromatography (ethyl acetate/CH2Cl2, 1:2) toprovide compound 6 as a yellow foam.General procedure: 3-Hydroxybenzaldehyde (61 mg, 0.5 mmol) was dissolved in 5mL of THF and cooled to 0 C under ice bath, and then DIAD(182 mg, 0.9 mmol) was added. After stirred at 0 C for 20 min, tertbutyl(2-hydroxyethyl)carbamate (145 mg, 0.9 mmol) and Ph3P(236 mg, 0.9 mmol) were added and the reaction was stirred at rtfor 16 h. Water (20 mL) was added and the reaction was extractedwith CH2Cl2 (3 x 10 mL). The combined organic layer was washedwith water, dried over Na2SO4, filtered, and concentrated in vacuo.The residue was purified by silica column chromatography (ethylacetate/CH2Cl2, 1:2) to give the key intermediate 39a.Following method E, l-[[4-(chloromethyl)phenyl]methyl]-N-[(3-fluoro-4-methoxy-2-pyridyl)methyl]-3- (methoxymethyl)pyrazole-4-carboxamide (318 mg, 1.0 mmol) was reacted with 2-hydroxypyridine-3- carbaldehyde (152 mg, 1.2 mmol) in a mixture of THF (10 mL) and DMF (3 mL), at 70 C for 72hrs. Standard work up and purification afforded the title compound (356 mg, 0.8 mmol, 83% yield) as a beige solid. (0571) [M+H]+ = 396.1 (0572) 1H NMR (CDCIs, 400 MHz) 3.47 (3H, s), 3.79 (3H, s), 4.71 (2H, s), 5.18 (2H, s), 5.28 (2H, s), 6.24 - 6.45 (1H, m), 7.25 (2H, d, J = 8.6 Hz), 7.33 (2H, d, J = 8.1 Hz), 7.59 (1H, dd, J = 6.6, 2.2 Hz), 7.80 (1H, s), 8.03 (1H, dd, J = 7.1, 2.2 Hz), 10.35 (1H, d, J = 0.8 Hz)

Molecular Weight:123.11
XLogP3:-0.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:123.032028402
Monoisotopic Mass:123.032028402
Topological Polar Surface Area:46.2
Heavy Atom Count:9
Complexity:203
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes