Tetrabutylammonium Fluoride → 3-(3-Hydroxy-3-methylbut-1-ynyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

HRID 1505956Notes

Reaction equation

[OH:1][C:2]([CH3:29])([CH3:28])[C:3]#[C:4][C:5]1[CH:27]=[N:26][C:8]2[N:9](COCC[Si](C)(C)C)[C:10]3[CH:15]=[N:14][C:13]([C:16]#[N:17])=[CH:12][C:11]=3[C:7]=2[CH:6]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[OH:1][C:2]([CH3:29])([CH3:28])[C:3]#[C:4][C:5]1[CH:27]=[N:26][C:8]2[NH:9][C:10]3[CH:15]=[N:14][C:13]([C:16]#[N:17])=[CH:12][C:11]=3[C:7]=2[CH:6]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A solution of 3-(3-hydroxy-3-methylbut-1-ynyl)-9-(2-trimethylsilanyl-ethoxymethyl)dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (254 mg, 0.624 mmol) in THF (12 mL) was treated with TBAF (3.7 mL, 12.5 mmol) and heated to 60° C. for 24 h. The reaction mixture was allowed to cool to ambient temperature and the solvent removed in vacuo. The resultant residue was dissolved in DCM, absorbed onto silica gel, and purified by flash chromatography (Biotage, 25 g, 1-100% EtOAc in heptane). The light orange solid was further purified by preparative HPLC (5-85% MeCN in water (0.1% NH4OH) over 30 min, 35 mL/min) to afford the title compound as an off-white solid (21 mg, 12%). 1H NMR (DMSO-D6, 400 MHz,): 12.99 (s, 1H), 9.04 (s, 1H), 8.93 (s, 1H), 8.86 (d, J=2.0 Hz, 1H), 8.69 (d, J=2.0 Hz, 1H), 5.53 (s, 1H), 1.55 (s, 6H). LCMS (Method D): RT=9.66 min, M+H+=277.

Workup

temperatureto cool to ambient temperature
customthe solvent removed in vacuo
dissolutionThe resultant residue was dissolved in DCM
customabsorbed onto silica gel
custompurified by flash chromatography (Biotage, 25 g, 1-100% EtOAc in heptane)
customThe light orange solid was further purified by preparative HPLC (5-85% MeCN in water (0.1% NH4OH) over 30 min, 35 mL/min)

Sources & evidence

ORD record: ord-591c749fe6524f6a8bd284a8ccb34d60
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09216980B2

Reaction notes

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