2-cyclopentylacetaldehyde

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a manner similar to the method described in Example 1a, glycine tert-butyl ester (0.7 g, 5 mmol) was reacted with 2-cyclopentylacetaldehyde (Betapharma) (0.9 g, 8 mmol) in CH2Cl2 at room temperature for 20 h to give [2-cyclopentyl-eth-(E)-ylideneamino]-acetic acid tert-butyl ester as a colorless oil (1 g, 90%).

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methyl ester (prepared as in Example 1, 2.6 g, 8.3 mmol) in dry tetrahydrofuran (60 mL) at −78° C. was added freshly prepared lithium diisopropylamide [prepared by adding 1.6 M n-butyllithium in n-hexane (6.7 mL, 10.7 mmol) to a solution of diisopropylamine (1.6 mL, 11.3 mmol) in dry tetrahydrofuran (15 mL) at 0° C.] dropwise. The mixture was stirred at −78° C. for 5 min and then treated with cyclopentyl acetaldehyde (1.2 g, 10.7 mmol) dropwise. The resulting mixture was stirred at −78° C. for 1 h and then quenched with brine. The mixture was extracted with ethyl acetate (2×150 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by flash column chromatography (QingDao silica gel, 200-300 mesh, 15% ethyl acetate/hexanes) afforded 1-benzenesulfonyl-2-(2-cyclopentyl-1-hydroxy-ethyl)-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methyl ester as a colorless oil (730 mg, 21%): 1H NMR (400 MHz, CDCl3) δ ppm 1.26 (m, 2H), 1.53-1.68 (m, 4H), 1.73-2.16 (m, 5H, H), 3.50 (br, 1 H), 3.89 (s, 3H), 5.41 (dd, J=5.0 Hz, 8.1 Hz, 1H), 6.67 (s, 1H), 7.42 (brt, 2H), 7.53 (brt, 1H), 8.14 (br. d., 2H), 8.33 (m, 1H), 8.96 (m, 1H). prepared The resulting mixture was stirred at −78° C. for 1 h quenched with brine The mixture was extracted with ethyl acetate (2×150 mL) washed with brine dried over anhydrous sodium sulfate concentrated in vacuo Purification by flash column chromatography (QingDao silica gel, 200-300 mesh, 15% ethyl acetate/hexanes)