3-Methyl-1H-pyrrolo[2,3-b]pyridine

N'-(3, 4-Dimethoxybenzylidene)-3-(3-methyl-lH-pyrrolo[2, 3-b]pyridin-l- yl)propanehydrazide; [0516] (a) 3-Methyl-lH-pyrrolo[2, 3-b]pyridine: This intermediate was prepared using a similar method to that described by Jensen et. al., Angew. Chem. Int. Ed. 2008, 47, 888-890. To a reaction tube was added toluene (5 mL), 2, 3-dichloropyridine (300 mg, 2.03 mmol), PdA mixture of 2, 3-dichloropyridine (500mg), allylamine (0.254mL), NaOtBu (1.19g), PdA mixture of 2, 3-dichloropyridine (500 mg), allylamine (0.254 mL), NaOtBu (1.19 g), PdExample 40(2)3-Methyl-1H-pyrrolo[2, 3-b]pyridine (40b)Normal-butyllithium (2.69 M, 118.7 mL) was dropwise added to a solution of compound (40a) (32.4 g) in THF (500 mL) at an internal temperature of -30 to -10° C., followed by stirring at 0° C. for 30 min. Subsequently, a solution of DMF (11.18 g) in THF (50 mL) was added to the reaction solution at an internal temperature of -40° C., followed by increasing the temperature to room temperature. Then, 6 N hydrochloric acid (200 mL) was added to the reaction solution, followed by stirring at 60° C. for 2 hr. After cooling, ethyl acetate (200 mL) and water (100 mL) were added to the reaction solution for distribution. The aqueous layer was added to sodium hydroxide (4 M, 300 mL), and pH was adjusted to 12, followed by stirring for 1 hr. The precipitate was collected by filtration, washed by sprinkling water, and dried under reduced pressure to obtain compound (40b) (16.52 g, 86percent) as a white solid.To a solution of 3-methyl-lH-pyrrolo[2, 3-b]pyridine (1 g, 8 mmol) in THF (15 mL) was added DMAP (9.2 mg, 0.08 mmol) followed by the addition of di-fer/-butyl dicarbonate (2.48 g, 11.4 mmol). The reaction was stirred at -25 C under nitrogen for 20.5 h. Water (0.1 mL) was added to the reaction and stirring was continued at -25 C for 40 min. All solvents were removed in vacuo. The crude product was azeotroped with toluene (3 x 5 mL) to give the title compound as a tan solid (quanititative yield). The product was used without further purification. LC-MS retention time = 3.11 min; m/z = 255.10 [M+Na] +. (Column: Phenomenex Luna C18 50 x 2.0 mm 3 muiotaeta. Solvent A = 90% Water : 10% MeOH : 0.1% TFA. Solvent B = 10% Water : 90% MeOH : 0.1% TFA. Flow Rate = 0.8 mL/rnin. Start % B = 0. Final % B = 100. Gradient Time = 4 minutes, then a 1 minute hold at 100% B. Oven temperature = 40 C. Wavelength = 220 nm). NMR (400 MHz, DMSO-d6) delta 8.37 (dd, J=4.6, 1.6 Hz, IH), 7.98 (dd, J=7.8, 1.8 Hz, IH), 7.55 (d, J=1.3 Hz, IH), 7.27 (dd, J=7.8, 4.8 Hz, IH), 2.23 (d, J=1.3 Hz, 3H), 1.60 (s, 9H).

An azaindole derivative as CRTH2 receptor antagonist.