Sulfuric Acid → 3-[4-(4-Methylpiperazin-1-Yl)phenyl]-9h-Pyrrolo[2,3-B:5,4-C']dipyridine-6-Carboxylic Acid

HRID 1506000Notes

Reaction equation

Br[C:2]1[CH:17]=[N:16][C:5]2[NH:6][C:7]3[CH:12]=[N:11][C:10]([C:13]([OH:15])=[O:14])=[CH:9][C:8]=3[C:4]=2[CH:3]=1.[CH3:18][N:19]1[CH2:24][CH2:23][N:22]([C:25]2[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=2)[CH2:21][CH2:20]1.S(=O)(=O)(O)O>C(#N)C.C(=O)([O-])[O-].[Na+].[Na+].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:18][N:19]1[CH2:24][CH2:23][N:22]([C:25]2[CH:26]=[CH:27][C:28]([C:2]3[CH:17]=[N:16][C:5]4[NH:6][C:7]5[CH:12]=[N:11][C:10]([C:13]([OH:15])=[O:14])=[CH:9][C:8]=5[C:4]=4[CH:3]=3)=[CH:29][CH:30]=2)[CH2:21][CH2:20]1

Participants

Conditions

Temperature: 140 °C

Procedure

A degassed mixture of 3-bromo-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carboxylic acid (37.7 mg, 0.13 mmol), 4-(4-methylpiperazin-1-yl)phenylboronic acid, pinacol ester (58.5 mg, 0.194 mmol) and bis(triphenylphosphine)palladium(II) dichloride (4.5 mg, 6.4 μmol) in acetonitrile (2 mL) and aqueous sodium carbonate solution (2 mL) was heated under microwave irradiation at 140° C. for 10 minutes. The cooled reaction mixture was acidified with 10% aqueous sulfuric acid, filtered, and the crude solution was purified by preparative HPLC (0-30% MeCN over 30 min, 35 mL/min) to afford the title compound. 1H NMR (DMSO-D6, 400 MHz): 12.62 (s, 1H), 9.66 (s, 1H), 9.14-8.95 (m, 4H), 7.77 (d, J=8.7 Hz, 2H), 7.18 (d, J=8.9 Hz, 2H), 3.97 (d, J=13.4 Hz, 2H), 3.55 (d, J=11.6 Hz, 2H), 3.20 (q, J=11.1 Hz, 2H), 3.04 (t, J=11.9 Hz, 2H), 2.89 (s, 3H). LCMS (Method D): RT=5.09 min, M+H+=388.

Workup

customThe cooled reaction mixture
filtrationfiltered
customthe crude solution was purified by preparative HPLC (0-30% MeCN over 30 min, 35 mL/min)

Sources & evidence

ORD record: ord-eab726a907814887acb3825ddc24361c
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09216980B2

Reaction notes

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