Sodium Methoxide → HCID 178487634, compound

HRID 1672447Notes

Reaction equation

HRID 1672447 reaction equation
F[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[N:7][C:8]([NH:12][C@H:13]3[CH2:18][CH2:17][C@H:16]([OH:19])[CH2:15][CH2:14]3)=[N:9]2)=[CH:4][CH:3]=1.[CH3:20][O-:21].[Na+]>CO>[CH3:20][O:21][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[N:7][C:8]([NH:12][C@H:13]3[CH2:18][CH2:17][C@H:16]([OH:19])[CH2:15][CH2:14]3)=[N:9]2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 10942334Sodium MethoxideHCID 178521596HCID 178521596, compound

Product 1

HCID 178487634HCID 178487634, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of trans-4-[(7-fluoroquinazolin-2-yl)amino]cyclohexanol (800 mg, 3.06 mmol) in MeOH (25 mL) was added sodium methoxide powder (1.65 g, 30.62 mmol) and the solution heated to reflux for 16 hours under nitrogen. The mix was cooled and the solvents evaporated. The residue was diluted with water (100 mL), brine (50 mL) and extracted with DCM (4×150 mL), and the combined organics were dried over MgSO4, filtered and stripped. The residue was purified via Biotage flash chromatography (40M) eluting with 2-6% MeOH/DCM over 1300 mL to yield the title compound as an off white solid, 830 mg, 99%. 1H NMR (400 MHz, DMSO-D6) δ ppm 8.86 (1H, s) 7.63 (1H, d, J=8.84 Hz) 7.08 (1H, d, J=6.57 Hz) 6.78 (2H, dd, J=8.72, 2.15 Hz) 4.55 (1H, d, J=4.55 Hz) 3.86 (3H, s) 3.71-3.84 (1H, m) 3.35-3.50 (1H, m) 1.76-2.02 (4H, m) 1.14-1.42 (4H, m); MS (API+) for C15H19N3O2 m/z 274.2 (M+H)+.

Workup

  1. temperaturethe solution heated
  2. temperatureto reflux for 16 hours under nitrogen
  3. temperatureThe mix was cooled
  4. customthe solvents evaporated
  5. additionThe residue was diluted with water (100 mL), brine (50 mL)
  6. extractionextracted with DCM (4×150 mL)
  7. dry with materialthe combined organics were dried over MgSO4
  8. filtrationfiltered
  9. customThe residue was purified via Biotage flash chromatography (40M)
  10. washeluting with 2-6% MeOH/DCM over 1300 mL

Sources & evidence

ORD record
ord-ef8062c810724480b715f1d6658bede4
Source dataset
uspto-grants-2011_08
Patent number
US07998978B2

Reaction notes

Loading…