General procedure for the synthesis of 4-bromo-1H-indole-2-carboxamide from 4-bromo-1H-indole-2-carbonitrile:
1. 4-Bromo-1H-indole-2-carboxamide (207.3 mg, 0.87 mmol) was dissolved in ethyl acetate (8 mL) in a microwave vial.
2. To the above solution was added a 50% ethyl acetate solution (0.630 mL, 1.06 mmol) of 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphine-2,4,6-trioxide.
3. The vial was sealed and the mixture was placed in a microwave reactor and stirred at 100 °C for 1.5 hours.
4. reseal the vial and continue stirring in the microwave reactor at 100 °C for 2 hours.
5. A 50% ethyl acetate solution (0.250 mL, 0.42 mmol) of 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphine-2,4,6-trioxide was added again, the vial was resealed, and stirring was continued at 100 °C for 3.5 hours.
6. Upon completion of the reaction, water (10 mL) was added to the reaction mixture for stratification.
7. The aqueous layer was extracted with ethyl acetate (2 x 10 mL), the organic layers were combined and filtered through a cartridge containing hydrophobic glass material.
8. The filtrate was evaporated under vacuum to give a light yellow crystalline solid.
9. The solid was redissolved in DMSO (2 mL) and purified by MDAP (high pH).
10. The collected grades were evaporated under a stream of nitrogen, redissolved in methanol (~2 mL) and combined.
11. The solution was evaporated under a stream of nitrogen and the residue was vacuum dried to afford the target product 4-bromo-1H-indole-2-carbonitrile (145.0 mg, 0.66 mmol, 76% yield) as a glassy white solid.
12. LCMS (2 min high pH) analysis: retention time Rt = 1.14 min, [M-H]? = 219.0.
