Sulfuric Acid → 3-(3-Trifluoromethylphenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carboxylic acid

HRID 1506002Notes

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.[F:18][C:19]([F:30])([F:29])[C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][CH:25]=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>[F:18][C:19]([F:30])([F:29])[C:20]1[CH:25]=[C:24]([C:2]2[CH:17]=[N:16][C:5]3[NH:6][C:7]4[CH:12]=[N:11][C:10]([C:13]([OH:15])=[O:14])=[CH:9][C:8]=4[C:4]=3[CH:3]=2)[CH:23]=[CH:22][CH:21]=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 (20.0 mg, 68.5 μmol), 3-(trifluoromethyl)phenylboronic acid (19.5 mg, 0.103 mmol), and bis(triphenylphosphine)palladium(II) dichloride (2.4 mg, 3.4 μmol) in acetonitrile (0.3 mL) and 2N aqueous sodium carbonate solution (0.3 mL) was heated under microwave irradiation at 140° C. for 10 minutes. The cooled reaction mixture was acidified with 10% aqueous sulfuric acid. The solid was removed by filtration and the resultant filtrate was purified by preparative HPLC (5-45% MeCN over 45 min, 35 mL/min) to afford the title compound. 1H NMR (DMSO-D6, 400 MHz): 12.75 (s, 1H), 9.38-9.00 (m, 311), 8.21 (m, 1H), 7.78 (m, 2H), 7.65-7.60 (m, 2H). LCMS (Method D): RT=10.76 min, M+H+=358.

Workup

customThe cooled reaction mixture
customThe solid was removed by filtration
customthe resultant filtrate was purified by preparative HPLC (5-45% MeCN over 45 min, 35 mL/min)

Sources & evidence

ORD record: ord-60ebae9b5e804425ab48a27a087e3f31
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09216980B2

Reaction notes

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