Sodium Bicarbonate → 4-cyano-N-(4-(4-methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl)-1H-pyrrole-2-carboxamide

To 62 mg (0.44 mmol) of 4-cyano-1H-pyrrole-2-carboxylic acid (as prepared in Example 2) in dichloromethane (20 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (107 mg, 0.560 mmol), hydroxybenzotriazole (HOBt) (65 mg, 0.48 mmol), and 4-(4-methyl-piperazin-1-yl)-2-piperidin-1-yl-phenylamine (as prepared in Example 5, step (b), 100 mg, 0.370 mmol) and the mixture stirred for 24 h at RT. The mixture was poured into satd aq sodium bicarbonate (50 mL) and extracted with dichloromethane (2×20 mL). The organic layers were washed with brine (20 mL), dried over Na2SO4 and the solvent was removed in vacuo. Purification of the resulting residue by silica gel preparative TLC eluting with 10% methanol in dichloromethane yielded 63 mg (44%) of the title compound as a tan solid. 1H-NMR (400 MHz, CDCl3): δ 11.09 (br s, 1H), 9.11 (s, 1H), 8.25 (d, 1H, J=8.9 Hz), 7.45 (d, 1H, J=1.3 Hz), 6.88 (d, 1H, J=1.1 Hz), 6.81 (d, 1H, J=2.6 Hz), 6.75 (dd, 1H, J=8.9, 2.6), 3.21 (m, 4H), 2.84 (m, 4H), 2.62 (m, 4H), 2.38 (s, 3H), 1.78 (m, 5H). LC-MS (ESI, m/z): Calcd. for C22H29N6O, 393.2 (M+H); found: 393.2.

1. extractionextracted with dichloromethane (2×20 mL)
2. washThe organic layers were washed with brine (20 mL)
3. dry with materialdried over Na2SO4
4. customthe solvent was removed in vacuo
5. customPurification of the resulting residue by silica gel preparative TLC
6. washeluting with 10% methanol in dichloromethane

ORD record

ord-919e29eaeb484f9ba4f8c9096c1136f5

Source dataset

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07705042B2