Hydrogen Bromide → 3-Hydroxy-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

HRID 1505957Notes

Reaction equation

[OH:1][C:2]1[CH:24]=[N:23][C:5]2[N:6](COCC[Si](C)(C)C)[C:7]3[CH:12]=[N:11][C:10]([C:13]#[N:14])=[CH:9][C:8]=3[C:4]=2[CH:3]=1.Br.[OH-].[Na+].Cl>O1CCOCC1>[OH:1][C:2]1[CH:24]=[N:23][C:5]2[NH:6][C:7]3[CH:12]=[N:11][C:10]([C:13]#[N:14])=[CH:9][C:8]=3[C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 75 °C

Procedure

A solution of 3-hydroxy-9-(2-trimethylsilanylethoxymethyl)-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (90.9 mg, 0.267 mmol) in 1,4-dioxane (500 μL) was treated with 48% aqueous hydrobromic acid (500 μL) and heated at 75° C. for 10 min. The cooled reaction mixture was basified to pH 12 with 6N aqueous sodium hydroxide solution and then adjusted to pH 7-9 with dropwise addition of 1N hydrochloric acid. The solid was collected via centrifugation, the aqueous supernate discarded, and the solid dissolved in 1-2 mL of DMSO and purified by preparative HPLC (0-30% MeCN in water (0.1% formic acid) over 30 min, 35 mL/min) to afford the title compound as an off-white solid (19 mg, 33%). 1H NMR (DMSO-D6, 400 MHz,): 12.51 (s, 1H), 9.94 (s, 1H), 8.94 (s, 1H), 8.87 (s, 1H), 8.32 (d, J=2.7 Hz, 1H), 8.08 (d, J=2.7 Hz, 1H). LCMS (Method E): RT=2.90 min, M+H+=211.

Workup

customThe cooled reaction mixture
customThe solid was collected via centrifugation
dissolutionthe solid dissolved in 1-2 mL of DMSO
custompurified by preparative HPLC (0-30% MeCN in water (0.1% formic acid) over 30 min, 35 mL/min)

Sources & evidence

ORD record: ord-a85a427941eb4bddbab646c4cc2b127d
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09216980B2

Reaction notes

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