Convenient Synthesis of tert‐Butyl Esters of Indole‐5‐carboxylic Acid and Related Heterocyclic Carboxylic Acids

Convergent and enantioselective syntheses of cytosolic phospholipase A2α inhibiting N-(1-indazol-1-ylpropan-2-yl)carbamates

“…1 H NMR (300 MHz, CDCl 3 ): δ 0.87 (t, J = 6.7 Hz, 3H), 1. 15 (R)-Allyl 1-{2-[(tert-butoxycarbonyl)amino]-3-(4-octylphenoxy)-propyl}indazole-5-carboxylate ((R)-22). To a solution of allyl indazole-5-carboxylate (15) (0.114 g, 0.56 mmol) in dry DMF (5 mL) was added sodium hydride (60% dispersion in mineral oil) (0.024 g, 0.60 mmol).…”

“…Starting material was indazole-5-carboxylic acid (5), which first was converted into its tert-butylester 8 employing a reaction sequence published for the synthesis of tert-butyl benzotriazole-5-carboxylate. 15 Treatment of 8 with epichlorohydrin in presence of KOH and tetrabutylammonium bromide led to 9, which was reacted with 4-octylphenol to obtain the secondary alcohol 10. The alcohol functionality of this compound was converted to a mesylate (11) by reaction with methanesulfonyl chloride.…”

“…In Scheme 2, an alternative approach for the synthesis of 4 is outlined, which is more convergent in respect of the variation of the octylphenoxy-part of 4 during the course of structure-activity studies. This synthetic route started from indazole-5-carboxylic acid, which was converted into its allyl ester (15) by reaction with allyl bromide in presence of K 2 CO 3 . Using Cs 2 CO 3 as base, the indazole ester 15 was alkylated with epichlorohydrin in position 1 yielding the oxiranylmethylindazole derivative 16.…”

“…) as mobile phase at a flow rate of 1 mL min −1 . The detection wavelength was 254 nm.Allyl indazole-5-carboxylate(15). To a stirring suspension of potassium carbonate (0.52 g, 3.76 mmol) in dry DMF (4 mL) were added allyl bromide (2.2 mL, 13 mmol) and indazole-5-carboxylic acid (0.150 g, 0.93 mmol) and the obtained mixture was stirred at room temperature for 3 h. After addition of water (15 mL), the reaction mixture was exhaustively extracted with ethyl acetate.…”

1-Benzylindoles as inhibitors of cytosolic phospholipase A2α: synthesis, biological activity, aqueous solubility, and cell permeability

“…The combined organic phases were washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (cyclohexane to cyclohexane/ethyl acetate, 93 : 7) to give 36 as a solid (25 26 (103 mg, 0.47 mmol) in dry DMF (10 mL) was treated under a nitrogen atmosphere and cooled in an ice bath with sodium hydride (60% dispersion in mineral oil) (19 mg, 0.47 mmol) and stirred for 30 min at room temperature. After addition of 34 (180 mg, 0.47 mmol), the mixture was stirred for another 18 h. The reaction mixture was diluted with water and exhaustively extracted with ethyl acetate.…”