4-BROMO-PYRIDINE-2-CARBOXYLIC ACID METHYL ESTER

yellow solid

Methyl 4-bromopyridine-2-carboxylate (147) Methyl 4-bromopyridine-2-carboxylate (147); A solution of 4-bromopyridine hydrochloride (595 mg, 3.06 mmol) in DCM(20 mL) is washed with aqueous NaHCOSynthesis of Compound R5; Methyl 4-bromopyridine-2-carboxylate (147); A solution of 4-bromopyridine hydrochloride (595 mg, 3.06 mmol) in DCM(20 mL) is washed with aqueous NaHCOTo a solution of 4-bromopyridine-2-carboxylic acid (0.5 g, 2.5 mmol, Apollo Scientific) in a mixture of ethyl acetate (15 mL) and methanol (1.5 mL), was added dropwise a solution of trimethylsilyldiazomethane (3.7 mL, 2 M in diethyl ether, 7.4 mmol), at about 0° C. After the addition was complete the temperature was raised to rt and the mixture stirred for about another 1.5 h at rt. The resulting mixture was concentrated in vacuo and diethyl ether (25 mL) was added to the residue. The resulting mixture was filtered and concentrated in vacuo. The residue was purified by column chromatography (SiOΛ/-Hydroxy-4-(pyridin-3-ylethynyl)pyridine-2-carboxamide; A. Methyl 4-bromopyridine-2-carboxylate; To a solution of 4-bromopyridine-2-carboxylic acid (0.5 g, 2.5 mmol) in ethyl acetate (15 niL) was added TMS-diazomethane (3.7 mL, 7.4 mmol, 2.0 M solution in THF) over a period of 5 min at 0 70A: 4-Bromopicolinic acid (127.5 mg, 0.63 mmol) was dissolved in a mixture of 1 mL of THF and 300 /L of methanol and cooled at 0°C. Trimethylsilyldiazomethane (276 L, 1.87 mmol) was added dropwise at 0°C (strong gas evolution). The solution was stirred for 2 hours at 0°C, then over night at room temperature. A few drop of acetic acid were then added followed by water. The aqueous solution was extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated in vacuo. Compound 70A was obtained as a yellow oil (71 mg, 60percent yield). NMR (ppm, CDC1Step 1 To a solution of dioxane: 2 M K2CO3 (1:1, 116 ml total) was added Under nitrogen, a solution of 5-[1-(hydroxymethyl)-2, 3-dihydro-1H-isoindol-2-yl]-4-(trifluoromethyl)-2-[[2-(trimethylsilyl)ethoxy]methyl]-2, 3-dihydropyridazin-3-one (500 mg, 1.13 mmol, 1.00 equiv), [Pd(allyl)Cl]2 (42 mg, 0.10 equiv), Rockphos (53 mg, 0.10 equiv), Cs2CO3 (1.1 g, 3.38 mmol, 3.00 equiv) and A solution of 5-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(trifluoromethyl)-2-[[2-(trimethylsilyl)ethoxy]methyl]-2, 3-dihydropyridazin-3-one (360 mg, 0.91 mmol, 1.00 equiv), [Pd(allyl)Cl]2 (35.519 mg, 0.10 equiv), Rockphos (42.94164 mg, 0.09 mmol, 0.10 equiv),

Molecular Weight:216.03
XLogP3:1.7
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:214.95819
Monoisotopic Mass:214.95819
Topological Polar Surface Area:39.2
Heavy Atom Count:11
Complexity:151
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes