Neopentyl alcohol → HCID 89783444, compound

HRID 1055970Notes

Reaction equation

HRID 1055970 reaction equation
[H-].[Na+].[CH2:3]([OH:8])[C:4]([CH3:7])([CH3:6])[CH3:5].F[C:10]1[C:11]([CH3:30])=[N:12][C:13]2[C:18]([N:19]=1)=[C:17]([C:20]1[NH:28][C:27]3[CH2:26][CH2:25][NH:24][C:23](=[O:29])[C:22]=3[CH:21]=1)[CH:16]=[CH:15][CH:14]=2.CO.C(Cl)Cl>CN(C=O)C.[NH4+].[Cl-]>[CH3:30][C:11]1[C:10]([O:8][CH2:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[N:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][C:17]=2[C:20]2[NH:28][C:27]3[CH2:26][CH2:25][NH:24][C:23](=[O:29])[C:22]=3[CH:21]=2)[N:12]=1

Participants

7

Reactant 4

HCID 6404Neopentyl alcoholHCID 24758Sodium hydrideHCID 21226129Dichloromethane methanolHCID 897833202-(3-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 89783444HCID 89783444, compoundYield 31.1%

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 neopentyl alcohol (Aldrich; 0.103 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 100° C. for 17 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-(2-methyl-3-(neopentyloxy)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (15.3 mg, 0.042 mmol, 31% yield) as a yellow solid: 1H NMR (400 MHz, CDCl3) δ ppm 12.03 (1H, br. s.), 8.00 (1H, d, J=7.6 Hz), 7.79 (1H, d, J=8.0 Hz), 7.56 (1H, t, J=7.8 Hz), 7.18 (1H, d, J=2.0 Hz), 5.43 (1H, br. s.), 4.12 (2H, s), 3.68 (2H, td, J=6.5, 1.4 Hz), 2.96 (2H, t, J=6.8 Hz), 2.71 (3H, s), 1.18 (9H, s). m/z (ESI, +ve) 365.1 (M+H)+.

Workup

  1. temperaturethe resulting solution was heated at 100° C. for 17 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-be5f632a80204aca93e525247e460857
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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