Sodium Carbonate → HCID 9949459, compound

HRID 365374Notes

Reaction equation

HRID 365374 reaction equation
[CH:1]1([C:4]#[C:5][C:6]2([C:19]([F:22])([F:21])[F:20])[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([F:17])[C:14]=3[F:16])[NH:9][C:8](=O)[NH:7]2)[CH2:3][CH2:2]1.C([O-])([O-])=O.[Na+].[Na+].NC(N)=[S:31]>P(Cl)(Cl)(Cl)=O>[CH:1]1([C:4]#[C:5][C:6]2([C:19]([F:22])([F:21])[F:20])[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([F:17])[C:14]=3[F:16])[NH:9][C:8](=[S:31])[NH:7]2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 474058214287-71-5HCID 2723790Thiourea

Product 1

HCID 9949459HCID 9949459, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Conditions

Temperature
95 °C

Procedure

A solution of (+/-)-4-cyclopropylethynyl-5,6-difluoro-4-trifluoromethyl-3,4-dihydro-2(1H)-quinazolinone (0.32 g, 1.0 mmol) in phosphorous oxychloride (5 mL) containing Na2CO3 (160 mg, 1.5 mmol) was heated at 95° C. overnight. After cooling to room temperature, the phosphorus oxychloride was removed under reduced pressure. The residue was dissolved in ethanol (5 mL) and thiourea (0.44 g, 5.7 mmol) was added. The resulting mixture was heated at reflux for 24 hours, cooled to room temperature and concentrated. The material was dissolved in EtOAc (75 mL) and washed sequentially with saturated aqueous NaHCO3 (50 mL) and saturated aqueous NaCl (50 mL). The organic extract was dried over MgSO4, filtered and concentrated. The crude material was purified by flash chromatography (38% EtOAc/hexanes) to afford the title compound as a white solid (142 mg, 43%): mp 241-243° C.; 1H NMR (300 MHz, acetone-d6) δ 7.52-7.43 (m, 1H), 7.06-7.03 (m, 1H), 1.43-1.40 (m, 1H), 0.89-0.86 (m, 2H), 0.79-0.74 (m, 2H); 19F NMR (282 MHz, acetone-d6) δ -83, -136, -145; Analysis calc'd for C14H9F5N2S: C, 50.60; H, 2.73; N, 8.43; found: C, 50.46; H, 2.78; N, 8.31.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe phosphorus oxychloride was removed under reduced pressure
  3. dissolutionThe residue was dissolved in ethanol (5 mL)
  4. temperatureThe resulting mixture was heated
  5. temperatureat reflux for 24 hours
  6. temperaturecooled to room temperature
  7. concentrationconcentrated
  8. dissolutionThe material was dissolved in EtOAc (75 mL)
  9. washwashed sequentially with saturated aqueous NaHCO3 (50 mL) and saturated aqueous NaCl (50 mL)
  10. extractionThe organic extract
  11. dry with materialwas dried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe crude material was purified by flash chromatography (38% EtOAc/hexanes)

Sources & evidence

ORD record
ord-962aa5286f9c4278aaf31262ee48009f
Source dataset
uspto-grants-2000_10
Patent number
US06127375

Reaction notes

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