Sodium Carbonate → 5-Cyano-2-pyridin-3-yl-indole-1-carboxylic acid tert-butyl ester

A mixture of 1-Boc-5-cyanoindole-2-boronic acid (339 mg, 1.19 mmol), 3-bromo-pyridine (150 mg, 93 uL, 0.95 mmol), aqueous sodium carbonate (2M, 0.95 mL, 1.9 mmol) and DME (4 mL) is degassed with nitrogen and PS—Pd(PPh3) (285 mg, 0.11 mmol/g, 0.028 mmol) is added. The resulting mixture is then heated in the microwave at 120° C. for 20 min and at 130° C. for 25 min (three times). The reaction mixture is filtered through a sintered funnel and washed with dichloromethane (50 mL). The filtrate is dried over Na2SO4, filtered, and concentrated. The residue is purified by reverse phase HPLC (5 to 80% acetonitrile-0.1% aqueous ammonia) to give 5-cyano-2-pyridin-3-yl-indole-1-carboxylic acid tert-butyl ester as a solid. 1H NMR (400.3 MHz, CDCl3) δ ppm 1.34 (s, 9H), 6.67 (s, 1H), 7.39 (dd, J=4.9, 7.8 Hz, 1H), 7.61 (dd, J=1.6, 8.7 Hz, 1H), 7.74 (m, 1H), 7.92 (s, 1H), 8.35 (d, J=8.7 Hz, 1H), 8.65 (dd, J=1.6 Hz, 4.9 Hz, 1H), 8.69 (d, J=2.2 Hz, 1H). MS (ESI) m/z 320 (M+H)+.

1. additionis added
2. filtrationThe reaction mixture is filtered through a sintered funnel
3. washwashed with dichloromethane (50 mL)
4. dry with materialThe filtrate is dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue is purified by reverse phase HPLC (5 to 80% acetonitrile-0.1% aqueous ammonia)

ORD record

ord-2fb68e1a6b72441288eca4f561357924

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08791141B2