ChemicalBook CAS DataBase List 1H-PYRROLO[3,2-B]PYRIDINE-2-CARBOXYLIC ACID

1H-PYRROLO[3,2-B]PYRIDINE-2-CARBOXYLIC ACID synthesis

14synthesis methods

Product Name:1H-PYRROLO[3,2-B]PYRIDINE-2-CARBOXYLIC ACID
CAS Number:17288-35-6
Molecular formula:C8H6N2O2
Molecular Weight:162.15

1H-Pyrrolo[3,2-b]pyridine-2-carboxylic acid ethyl ester

17288-32-3

1H-PYRROLO[3,2-B]PYRIDINE-2-CARBOXYLIC ACID

17288-35-6

General procedure for the synthesis of 4-azaindole-2-carboxylic acid from ethyl 4-azaindole-2-carboxylate: 3-amino-2-chloropyridine (150 mg, 1.17 mmol), ethyl pyruvate (0.25 mL, 2.00 mmol), pyridinium p-toluenesulfonate (73 mg, 0.29 mmol), and tetraethoxysilane (0.26 mL, 1.18 mmol) were suspended in 0.4 mL of pyridine and stirred at 20 °C for 24 hours. Tetrakis(triphenylphosphine)palladium (70 mg, 0.06 mmol) and N,N-dicyclohexylmethylamine (0.35 mL, 2.06 mmol) were subsequently added, and the reaction mixture was placed in a microwave reactor, heated to 160 °C, and held for 20 min. After completion of the reaction, the reaction mixture was diluted with 100 mL of dichloromethane and extracted twice with 50 mL of half-saturated aqueous sodium bicarbonate. The organic layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (P3) to afford ethyl 1H-pyrrolo[3,2-b]pyridine-2-carboxylate (190 mg, 1.00 mmol). The ester was dissolved in a mixture of 17 mL ethanol and 5 mL water and lithium hydroxide (120 mg, 5.00 mmol) was added. After 16 hours of reaction, the pH of the reaction mixture was adjusted to 4 and the solvent was evaporated under vacuum. The crude product was purified by acidic ion exchange resin (Strata-X-C, Phenomenex) to afford 4-azaindole-2-carboxylic acid (155 mg, 82% yield). Product purity >95%; mass spectrum (ESI) m/z 163 (M + H)+; 1H NMR (DMSO) δ (ppm) 13.34 (br, 1H), 8.77 (d, J = 5.3 Hz, 1H), 8.53 (d, J = 8.3 Hz, 1H), 7.73 (dd, J = 5.4 Hz, J = 8.3 Hz, 1H), 7.33 ( br, 1H); 13C NMR (500 MHz, DMSO) δ (ppm) 161.4 (s), 138.0 (s), 136.1 (s), 135.8 (s), 132.7 (s), 128.6 (s), 119.6 (s), 101.2 (s).

17288-32-3
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$26.00/250mg

17288-35-6
96 suppliers
$21.00/100mg

Yield: 82%

Reaction Conditions:

Stage #1:1H-pyrrolo[3,2-b]pyridine-2-carboxylic acid ethyl ester with lithium hydroxide in ethanol;water for 16 h;
Stage #2: in ethanol;water; pH=4Acidic conditions;

Steps:

4.2.2.1. 1H-Pyrrolo[3,2-b]pyridine-2-carboxylic acid (5f)
3-Amino-2-chloro-pyridine 4f (150 mg, 1.17 mmol), ethyl pyruvate 8 (0.25 ml, 2.00 mmol), pyridinium p-toluenesulfonate, (73 mg, 0.29 mmol) and tetraethoxy-silane (0.26 ml, 1.18 mmol) were suspended in 0.4 ml pyridine and stirred for 24 h at 20 °C. Afterwards Pd[P(C₆H₆)₃]₄ (70 mg, 0.06 mmol) and N,N-dicyclohexylmethylamine (0.35 ml, 2.06 mmol) were added and the reaction mixture was heated in a microwave oven to 160 °C for 20 min. The reaction mixture is diluted with 100 ml dichloromethan and extracted two times with 50 ml of a half saturated aqueous sodium hydrogencarbonat solution. The organic layer was dried with sodium sulfate, the solvent was evaporated under reduced pressure and the crude product was purified using chromatography method P3, yielding 190 mg (1.00 mmol) of 1H-Pyrrolo[3,2-b]pyridine-2-carboxylic acid ethyl ester. The ester was dissolved in 17 ml ethanol and 5 ml water. To this solution lithium hydroxide (120 mg, 5.00 mmol) was added. After 16 h the pH value of the reaction mixture was adjusted to pH 4 and the solvent is evaporated in vacuum. The crude product was purified using an acid ion exchanger (Strata-X-C, Phenomenex), yielding of 155 mg (82%) of the title compound. Purity by method A1: >95%; MS (ESI) m/z 163 (M + H)⁺; ¹H NMR (DMSO) δ (ppm) 13.34 (br, 1H), 8.77 (d, J = 5.3 Hz, 1H), 8.53 (d, J = 8.3 Hz, 1H), 7.73 (dd, J = 5.4 Hz, J = 8.3 Hz, 1H), 7.33 (br, 1H); ¹³C NMR (500 MHz, DMSO) δ (ppm) 161.4 (s), 138.0 (s), 136.1 (s), 135.8 (s), 132.7 (s), 128.6 (s), 119.6 (s), 101.2 (s).

References:

Engelhardt, Harald;De Esch, Iwan J.P.;Kuhn, Daniel;Smits, Rogier A.;Zuiderveld, Obbe P.;Dobler, Julia;Mayer, Moriz;Lips, Sebastian;Arnhof, Heribert;Scharn, Dirk;Haaksma, Eric E.J.;Leurs, Rob [European Journal of Medicinal Chemistry,2012,vol. 54,p. 660 - 668] Location in patent:experimental part