2-Thiazolecarboxylic acid, 4-[5-broMo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-, ethyl ester synthesis

Yield:1046793-41-2 57%

Reaction Conditions:

with sodium hydroxide;tetra(n-butyl)ammonium hydrogensulfate in dichloromethane;water at 20; for 1.5 h;

Steps:

4-(l-Benzenesulfonyl-5-bromo-lH-pyrrolo[2,3-b]pyridin-3-yl)-thiazole-2- carboxylic acid ethyl ester (III-a)(XXIII-a) ll-a)Compound (XXIII-a) (6.08 g, 14.0 mmol), W-Bu₄NHSO₄ (100 mg, cat.), PhSO₂Cl (2.50 mL, 19.5 mmol) and 50% aqueous NaOH (2 mL) in CH₂Cl₂ (75 mL) were reacted at RT for 1.5 h following the general procedure for the protection of (XXIII). The crude product was recystallized from CH₂Cl₂/hexane to afford pure (III-a) (2.33 g) as a yellow solid. More product was obtained from the mother liquor by SGC using hexane:CH₂Cl₂:Et0Ac (2: 1 : 1, v/v/v) as eluent. Total yield of (III-a) (4.40 g, 8.94 mmol, 57%). ¹U NMR (400 MHz, CDCl₃) δ 1.51 (t, J = 7.2 Hz, 3H), 4.55 (q, J = 7.1 Hz, 2H), 7.53 (t, J = 7.8 Hz, 2H), 7.63 (t, J = 7.5 Hz, IH), 7.74 (s, IH), 8.24 (d, J = 7.8 Hz, I H), 8.30 (s, IH), 8.54 (d, J= 2.1 Hz, 1 H), 8.56 (d, J= 2.1 Hz, I H).; General procedure for protection of (XXIII)(XXIII) (III) To a stirred solution of (XXIII) (10 mmol) in CH₂Cl₂ (53 mL) was added n- Bu₄NHSO₄ (71 mg - 500 mg, 0.21 mmol - 1.47 mmol) and 50% aqueous NaOH (1.4 mL). PhSO₂Cl (1.8 mL, 14 mmol) was then added dropwise, and the reaction stirred at RT for 1.5 h. The mixture was then diluted with EtOAc (290 mL) and acetone (14 mL), washed with brine (2 x 70 mL) and concentrated to give crude (III). This product can be purified by SGC using appropriate solvent system as eluent or recrystallized from CH₂Cl₂/hexane to afford pure (III). Additional product was obtained from the mother liquors by purification by SGC. Total yield of (III) 40-60%. The same procedure can be applied for protection of (XXVI) to afford (IX).

References:

WO2008/95943,2008,A1 Location in patent:Page/Page column 54-55; 164