3-Fluorophenol → HCID 89783498, compound

HRID 1055872Notes

Reaction equation

[H-].[Na+].[F:3][C:4]1[CH:5]=[C:6]([OH:10])[CH:7]=[CH:8][CH:9]=1.Cl[C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[C:15]([C:22]3[NH:30][C:29]4[CH2:28][CH2:27][NH:26][C:25](=[O:31])[C:24]=4[CH:23]=3)[CH:16]=[CH:17][CH:18]=2)[N:13]=1>>[F:3][C:4]1[CH:5]=[C:6]([CH:7]=[CH:8][CH:9]=1)[O:10][C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[C:15]([C:22]3[NH:30][C:29]4[CH2:28][CH2:27][NH:26][C:25](=[O:31])[C:24]=4[CH:23]=3)[CH:16]=[CH:17][CH:18]=2)[N:13]=1

Participants

Reactant 3

HCID 97433-Fluorophenol

HCID 24758Sodium hydride

HCID 897835482-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 89783498HCID 89783498, compoundYield 17.9%

Conditions

Temperature: 85 °C

Procedure

Prepared according to Example 103, using NaH as a 60% dispersion in mineral oil (47.0 mg, 1.176 mmol, Sigma Aldrich), 3-fluorophenol (108 μl, 1.176 mmol, Sigma Aldrich), and 2-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 1; 50 mg, 0.168 mmol) and heating to 85° C. for 17 h. Purification by reverse-phase HPLC (Phenomenex Gemini column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in ACN/H2O, gradient 5% to 90%) to provide 2-(2-(3-fluorophenoxy)-8-quinolinyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one (11.2 mg, 11%) as the free base following filtration through a Si-carbonate cartridge (Silicyle) with MeOH. 1H NMR (400 MHz, MeOH-d4) δ ppm 7.10 (1H, m) 7.10 (1H, d, J=1.00 Hz) 6.80-6.87 (1H, m) 6.82 (1H, d, J=1.00 Hz) 6.44-6.49 (1H, m) 6.31-6.38 (1H, m) 6.16-6.24 (1H, m) 6.01-6.07 (1H, m) 5.87-5.99 (2H, m) 5.73 (1H, s) 2.23 (2H, t, J=1.00 Hz) 1.26 (2H, t, J=1.00 Hz). m/z (ESI, +ve) 374.1 (M+H)+.

Workup

customPrepared
customPurification by reverse-phase HPLC (Phenomenex Gemini column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in ACN/H2O, gradient 5% to 90%)

Sources & evidence

ORD record: ord-ab5490ee3a134a689bc79b985bde777c
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394297B2

Reaction notes

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