ethyl 5-bromo-1H-indole-2-carboxylate

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

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

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

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

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: Oxalyl chloride (3.43 mL, 39.9 mmol) was added with stirring to DMF (30 mL) and CH2Cl2 (80 mL) at 0° C. After 20 min at 0° C., 5-bromoindole-2-carboxylic acid ethyl ester (10 g, 37.3 mmol) in DMF (80 mL), was added. The mixture was stirred at rt for 24 h and poured into NaHCO3 (aq, sat) and extracted with CH2Cl2. The combined extracts were washed with H2O and brine, dried (Na2SO4) and concentrated. Crystallisation from EtOH gave the sub-title compound. Yield 8.9 g (81%). extracted with CH2Cl2 The combined extracts were washed with H2O and brine dried (Na2SO4) concentrated Crystallisation from EtOH

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

Procedure: A mixture of 5-bromoindole-2-carboxylic acid ethyl ester (4.22 g, 16 mmol), 4-trifluoromethylphenylboronic acid (4.50 g, 24 mmol), K3PO4 (11.7 g, 55 mmol), Pd(OAc)2 (176 mg, 0.78 mmol), tri-o-tolylphosphine (478 mg, 1.6 mmol), EtOH (20 mL) and toluene (90 mL) was stirred under argon for 20 min at rt, heated at 100° C. for 2 h, cooled and poured into NaHCO3 (aq, sat). The mixture was extracted with EtOAc and the combined extracts were washed with H2O and brine, dried (Na2SO4), concentrated and purified by chromatography to give the sub-title compound. Yield 3.91 g (75%). heated at 100° C. for 2 h cooled The mixture was extracted with EtOAc the combined extracts were washed with H2O and brine dried (Na2SO4) concentrated purified by chromatography

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

Procedure: To a solution of 5 g (19 mmol) of 5-bromoindol-2-carboxylic acid ethyl ester in 20 mL of anhydrous DMF was added portionwise 1.06 g (24 mmol) of NaH (55% in oil). The mixture was stirred at RT for 45 minutes, treated dropwise with 2.9 mL (24 mmol) of benzyl bromide and stirred for three hours. After addition of a saturated aqueous solution of NH4Cl and Et2O, the phases were separated and the aqueous one was extracted with Et2O. The combined organic phases were dried over Na2SO4 and evaporated to yield 6.7g (98%) of crude 5-bromo-1-benzylindole-2-carboxylic acid ethyl ester, orange oil, MS: 358 (MH+). stirred for three hours the phases were separated the aqueous one was extracted with Et2O The combined organic phases were dried over Na2SO4 evaporated

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

Procedure: To a stirring solution of 5-bromo-1H-indole-2-carboxylic acid ethyl ester (2.68 g, 10 mmol, ICN) in dry dimethylsulfoxide (42 ml) at room temperature under nitrogen was added sodium hydride (264 mg, 11 mmol) as a slurry in hexane in four equal portions over about ten minutes. 4-Nitrobenzyl bromide (2.16 g, 10 mmol) in dry dimethylsulfoxide (12 ml) was added dropwise over about five minutes. The mixture was stirred 2 hours, poured into water (50 ml) and extracted with ethyl acetate. The solution was washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was flash chromatographed on silica gel (110 g, methylene chloride) to give the title compound (3.28 g). extracted with ethyl acetate The solution was washed with brine dried over sodium sulfate filtered concentrated in vacuo chromatographed on silica gel (110 g, methylene chloride)

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

Procedure: In the same manner as that of Example 32, 4,5-diisopropylfuran-2-carboxamide (71 mg, 0.364 mmol) and ethyl 5-bromoindole-2-carboxylate (195 mg, 0.728 mmol) were coupled. The reaction mixture was treated in a conventional manner, and the resultant was purified by silica gel chromatography [hexane-ethyl acetate (4:1), and 1% methanol-chloroform] and then recrystallized to obtain ethyl 5-[(4,5-diisopropylfuran-2-carbonyl)amino]-2-indolecarboxylate (45 mg, 32%) as colorless prisms, together with the collected starting material (39 mg, 55%). The reaction mixture was treated in a conventional manner the resultant was purified by silica gel chromatography [hexane-ethyl acetate (4:1), and 1% methanol-chloroform] recrystallized

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

Procedure: In the same manner as that of Example 32, 4,5-diisopropylfuran-2-carboxamide (71 mg, 0.364 mmol) and ethyl 5-bromoindole-2-carboxylate (195 mg, 0.728 mmol) were coupled. The reaction mixture was treated in a conventional manner, and the resultant was purified by silica gel chromatography [hexane-ethyl acetate (4:1), and 1% methanol-chloroform] and then recrystallized to obtain ethyl 5-[(4,5-diisopropylfuran-2-carbonyl)amino]-2-indolecarboxylate (45 mg, 32%) as colorless prisms, together with the collected starting material (39 mg, 55%). The reaction mixture was treated in a conventional manner the resultant was purified by silica gel chromatography [hexane-ethyl acetate (4:1), and 1% methanol-chloroform] recrystallized