Sulfuric Acid → 3-(1-Methyl-1H-pyrazol-4-yl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carboxylic acid

HRID 1506001Notes

Reaction equation

C[O:2][C:3]([C:5]1[N:13]=[CH:12][C:11]2[NH:10][C:9]3[N:14]=[CH:15][C:16](Br)=[CH:17][C:8]=3[C:7]=2[CH:6]=1)=[O:4].[CH3:19][N:20]1[CH:24]=[C:23](B2OC(C)(C)C(C)(C)O2)[CH:22]=[N:21]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>[CH3:19][N:20]1[CH:24]=[C:23]([C:16]2[CH:15]=[N:14][C:9]3[NH:10][C:11]4[CH:12]=[N:13][C:5]([C:3]([OH:2])=[O:4])=[CH:6][C:7]=4[C:8]=3[CH:17]=2)[CH:22]=[N: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 methyl ester (30.4 mg, 99.3 μmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (31.0 mg, 0.149 mmol), and bis(triphenylphosphine)palladium(II) dichloride (3.5 mg, 5.0 μmol) in acetonitrile (2.5 mL) and 2N aqueous sodium carbonate solution (2.5 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 removed by filtration and the resultant filtrate purified by preparative HPLC (0-30% MeCN over 30 min, 35 mL/min) to afford the title compound. 1H NMR (DMSO-D6, 500 MHz): 12.84 (s, 1H), 9.04 (d, J=2.1 Hz, 1H), 8.95 (s, 2H), 8.91 (d, J=2.1 Hz, 1H), 8.25 (s, 1H), 8.00 (s, 1H), 6.48 (s, 1H), 3.92 (s, 3H). LCMS (Method D): RT=5.24 min, M+H+=294.

Workup

customThe cooled reaction mixture
customthe solid removed by filtration
customthe resultant filtrate purified by preparative HPLC (0-30% MeCN over 30 min, 35 mL/min)

Sources & evidence

ORD record: ord-18262a7123fe4d65acd88e7779efdc11
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09216980B2

Reaction notes

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