M-Cresol → HCID 89783205, compound

HRID 1055873Notes

Reaction equation

HRID 1055873 reaction equation
[H-].[Na+].[CH:3]1[C:8]([OH:9])=[CH:7][CH:6]=[CH:5][C:4]=1[CH3:10].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>CN(C=O)C>[CH3:10][C:4]1[CH:3]=[C:8]([CH:7]=[CH:6][CH:5]=1)[O:9][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

5

Reactant 3

HCID 342M-CresolHCID 24758Sodium hydrideHCID 897835482-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 89783205HCID 89783205, compoundYield 9.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Prepared according to Example 103, using NaH as a 60% dispersion in mineral oil (47.0 mg, 1.176 mmol, Sigma Aldrich) in DMF (1679 μl), m-cresol (123 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 16 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%) provided 2-(2-(3-methylphenoxy)-8-quinolinyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one (5.8 mg, 9.4%) as the free base following filtration through a Si-carbonate cartridge (Silicyle) with MeOH. 1H NMR (400 MHz, MeOH-d4) δ ppm 8.37-8.41 (1H, m) 8.10-8.14 (1H, m) 7.73-7.76 (1H, m) 7.46-7.56 (1H, m) 7.28-7.37 (2H, m) 7.14-7.22 (1H, m) 7.04 (3H, s) 3.48-3.55 (2H, m) 3.14-3.19 (2H, m) 2.47 (3H, s). m/z (ESI, +ve) 370.2 (M+H)+.

Workup

  1. customPrepared
  2. 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-49652bf99d4b4c3a99acf37cd509d7f5
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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