1H-indol-4-ylboronic acid

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:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-chloro-6-(4-methyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (72) (100 mg, 0.27 mmol), indole-4-boronic acid (1.1 eq., 48 mg), sodium hydrogen carbonate (3 eq., 69 mg) and bis(triphenylphosphine)palladium(II) chloride (0.05 eq., 10 mg) in toluene (2.5 mL), ethanol (1.5 mL) and water (0.7 mL) was flushed with argon and heated under microwave irradiation at 120° C. for 1 hour. The reaction mixture was partitioned between dichloromethane and water, organic layer was washed with brine, dried over magnesium sulfate, filtered and evaporated in vacuo. The resulting residue was purified using flash chromatography to yield the title compound 61 (23 mg, 19%). was flushed with argon The reaction mixture was partitioned between dichloromethane and water, organic layer was washed with brine dried over magnesium sulfate filtered evaporated in vacuo The resulting residue was purified

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of ethyl 2-iodo-5-(4-methoxyphenyl)oxazole-4-carboxylate (0.080 g, 0.15 mmol), indole-4-boronic acid (0.048 g, 0.30 mmol), Pd(dppf)2Cl2 (0.006 g, 0.007 mmol) and 1M aq. sodium carbonate (0.31 ml, 0.31 mmol) in acetonitrile (2.5 ml) was heated in the microwave at 150° C. for 15 minutes. The reaction mixture was diluted with DCM and washed with 1M NaOH. The organic phase was passed through a MP-SH cartridge, dried over MgSO4 and the solvent removed in vacuo to afford tert-butyl 4-(4-(4-(ethoxycarbonyl)-2-(1H-indol-4-yl)oxazol-5-yl)phenyl)piperazine-1-carboxylate which was used without further purification. LCMS (1) Rt: 2.61 min; m/z (ES+) 517. washed with 1M NaOH dried over MgSO4 the solvent removed in vacuo

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-indoleboronic acid (64 mg, 0.40 mmol) (from Step A above), (Z)-4-bromo-1,3-dihydro-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one (100 mg, 0.31 mmol) (Starting Material 7), and sodium carbonate (35 mg, 0.33 mmol) in 3 mL DME and 1 mL water was degassed for 15 min. by bubbling argon through the solution. Dichlorobis(triphenylphosphine)palladium (II) (13 mg) (Aldrich) was then added and the reaction was heated at 90° C. for 2 days. The reaction was then poured into 100 mL water and the product was extracted with ethyl acetate (4×50 mL). The combined organic layers were dried over magnesium sulfate and concentrated in vacuo. The product was purified via flash column chromatography (1% CH3OH in CHCl3) to yield 42 mg (38%) orange powder. by bubbling argon through the solution Dichlorobis(triphenylphosphine)palladium (II) (13 mg) (Aldrich) was then added The reaction was then poured into 100 mL water the product was extracted with ethyl acetate (4×50 mL) The combined organic layers were dried over magnesium sulfate concentrated in vacuo The product was purified via flash column chromatography (1% CH3OH in CHCl3)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of sodium hydride (130 mg, 5.41 mmol) in anhydrous tetrahydrofuran (20 mL) was added 4-bromoindole (973 mg, 4.96 mmol) (see Kosuge et al. supra) at 0° C. After 15 min. of stirring at 0° C., the reaction was cooled to −78° C., and tert-butyllithium (10.2 mmol, 1.7 M in hexane) (Aldrich) was added dropwise (a white precipitate immediately formed). After 10 min. tri-n-butylborate (2.75 mL, 10.2 mmol) (Aldrich) was added dropwise. The reaction was allowed to slowly warm to room temperature, then the suspension was poured into an ice cold solution of 1N HCl. The organic phase was separated, and the aqueous phase was washed with ether. The combined organic extracts were extracted with 1N NaOH (3×25 mL), and the combined alkaline extracts were acidified to pH 1 with 1N HCl. The product was then extracted with ether, and the combined ether layers were dried over magnesium sulfate and concentrated in vacuo to yield a brownish solid. The product was recrystallized from boiling water to yield 367 mg (46%) white crystals. the reaction was cooled to −78° C. immediately formed) to slowly warm to room temperature The organic phase was separated the aqueous phase was washed with ether The combined organic extracts were extracted with 1N NaOH (3×25 mL) The product was then extracted with ether the combined ether layers were dried over magnesium sulfate concentrated in vacuo to yield a brownish solid The product was recrystallized

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

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-(6-Bromo-1-methyl-1H-indazol-4-yl)-2-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-thiazole-4-carboxamide (100 mg, 0.215 mmol), 1H-indol-4-ylboronic acid (38.1 mg, 0.237 mmol), Pd(dppf)Cl2 (15.76 mg, 0.022 mmol) and tripotassium phosphate (137 mg, 0.646 mmol) were placed into a microwave vial with water (0.300 mL) and 1,4-dioxane (1.5 mL) and the mixture heated at 100° C. in a microwave for 10 mins. The solvent was blown off and the residue partitioned between water (10 ml) and DCM (10 ml). The organic layer was collected using a hydrophobic frit and the solvent blown off. The residue was purified by chromatography on silica eluting with 0-100% ethyl acetate in cyclohexane followed by 0-25% methanol to give the title compound. the residue partitioned between water (10 ml) and DCM (10 ml) The organic layer was collected The residue was purified by chromatography on silica eluting with 0-100% ethyl acetate in cyclohexane