Sodium hydride → HCID 89783464, compound

HRID 1055969Notes

Reaction equation

HRID 1055969 reaction equation
[H-].[Na+].[CH:3]1([OH:7])[CH2:6][CH2:5][CH2:4]1.F[C:9]1[C:10]([CH3:29])=[N:11][C:12]2[C:17]([N:18]=1)=[C:16]([C:19]1[NH:27][C:26]3[CH2:25][CH2:24][NH:23][C:22](=[O:28])[C:21]=3[CH:20]=1)[CH:15]=[CH:14][CH:13]=2.CO.C(Cl)Cl>CN(C=O)C.[NH4+].[Cl-]>[CH:3]1([O:7][C:9]2[C:10]([CH3:29])=[N:11][C:12]3[C:17]([N:18]=2)=[C:16]([C:19]2[NH:27][C:26]4[CH2:25][CH2:24][NH:23][C:22](=[O:28])[C:21]=4[CH:20]=2)[CH:15]=[CH:14][CH:13]=3)[CH2:6][CH2:5][CH2:4]1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 76218CyclobutanolHCID 21226129Dichloromethane methanolHCID 897833202-(3-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 89783464HCID 89783464, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
25 °C

Procedure

NaH (60% w/w in mineral oil; 37.8 mg, 0.945 mmol) was added to a solution of of cyclobutanol (Aldrich; 0.074 mL, 0.945 mmol) in DMF (1.0 mL) and the resulting suspension was stirred at 25° C. for 10 min. 2-(3-Fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 126; 40 mg, 0.135 mmol) was added, and the resulting solution was heated at 60° C. for 3 h. The mixture was cooled to 25° C., diluted with half-saturated aq. NH4Cl (30 mL), and extracted with DCM (2×40 mL). The combined organic extracts were washed with water (40 mL), dried over Na2SO4, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-100% EtOAc/hexanes, then 0-10% MeOH/DCM) furnished 2-(3-cyclobutoxy-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (17.8 mg, 0.051 mmol, 38% yield) as a yellow solid: 1H NMR (400 MHz, CDCl3) δ ppm 12.07 (1H, br. s.), 7.99 (1H, d, J=7.6 Hz), 7.78 (1H, d, J=7.2 Hz), 7.55 (1H, t, J=7.8 Hz), 7.18 (1H, d, J=2.0 Hz), 5.46 (1H, br. s.), 5.28 (1H, quin, J=7.4 Hz), 3.70 (2H, t, J=6.7 Hz), 3.02 (2H, t, J=6.8 Hz), 2.68 (3H, s), 2.59-2.67 (2H, m), 2.33-2.45 (2H, m), 2.01-2.13 (1H, m), 1.77-1.92 (1H, m). m/z (ESI, +ve) 349.2 (M+H)+.

Workup

  1. temperaturethe resulting solution was heated at 60° C. for 3 h
  2. temperatureThe mixture was cooled to 25° C.
  3. extractionextracted with DCM (2×40 mL)
  4. washThe combined organic extracts were washed with water (40 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customChromatographic purification of the residue (silica gel, 0-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-b4205b20e40e40f4884944e9b38e1bee
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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