Triethylamine → HCID 135873239, compound

HRID 1641415Notes

Reaction equation

HRID 1641415 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:9]=[O:10])=[CH:4][CH:3]=1.CCN(CC)CC.[OH:18][CH2:19][CH2:20][O:21][C:22]1[C:27]([CH3:28])=[CH:26][C:25]([C:29]2[NH:38][C:37](=[O:39])[C:36]3[C:31](=[CH:32][C:33]([O:42][CH3:43])=[CH:34][C:35]=3[O:40][CH3:41])[N:30]=2)=[CH:24][C:23]=1[CH3:44]>C1COCC1.CCOC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:10])[O:18][CH2:19][CH2:20][O:21][C:22]2[C:27]([CH3:28])=[CH:26][C:25]([C:29]3[NH:38][C:37](=[O:39])[C:36]4[C:31](=[CH:32][C:33]([O:42][CH3:43])=[CH:34][C:35]=4[O:40][CH3:41])[N:30]=3)=[CH:24][C:23]=2[CH3:44])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 709554-Fluorophenyl isocyanateHCID 135564749Apabetalone

Product 1

HCID 135873239HCID 135873239, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-fluorophenylisocyanate (0.138 mL, 1.14 mmol), Et3N (0.185 mL, 1.32 mmol) and 4 (0.0700 g, 0.189 mmol) in THF (1.00 mL) was heated at reflux for 8 hours. The mixture was cooled, diluted with EtOAc (200 mL), washed with saturated aqueous NH4Cl (3×75 mL), brine (75 mL), dried over Na2SO4, filtered and concentrated under vacuum. The residue was purified on silica gel (12 g, CH2Cl2/MeOH) and the product was freeze-dried from MeCN/H2O to provide 2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl 4-fluoro-phenylcarbamate (5) (0.0710 g, 74%) as a white solid: 1H NMR (300 MHz, DMSO-d6) δ 11.83 (s, 1H), 9.78 (s, 1H), 7.91 (s, 2H), 7.54-7.44 (m, 2H), 7.18-7.08 (m, 2H), 6.73 (d, J=2.31 Hz, 1H), 6.51 (d, J=2.31 Hz, 1H), 4.47-4.38 (m, 2H), 4.12-4.03 (m, 2H), 3.89 (s, 3H), 3.84 (s, 3H), 2.31 (s, 6H); MS (APCI) m/z 508 [C27H26FN3O6+H]+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 8 hours
  3. temperatureThe mixture was cooled
  4. washwashed with saturated aqueous NH4Cl (3×75 mL), brine (75 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified on silica gel (12 g, CH2Cl2/MeOH)
  9. dry with materialthe product was freeze-dried from MeCN/H2O

Sources & evidence

ORD record
ord-6305f7f5ffd14289b83d7a809c32be38
Source dataset
uspto-grants-2012_02
Patent number
US08114995B2

Reaction notes

Loading…