Chlorosulfonyl isocyanate → 8,9-Difluoro-5-methyl-6,7-dihydro-5H-pyrido[3,2,1-ij]quinazoline-1,3-dione

HRID 729408

Reaktionsgleichung

Reaktionsgleichung von HRID 729408
CO[C:3]([C:5]1[CH:6]=[C:7]([F:17])[C:8]([F:16])=[C:9]2[C:14]=1[NH:13][CH:12]([CH3:15])[CH2:11][CH2:10]2)=[O:4].ClS([N:22]=[C:23]=[O:24])(=O)=O.C([O-])(=O)C.[Na+].CC(C)([O-])C.[Na+]>ClCCl>[F:16][C:8]1[C:9]2[CH2:10][CH2:11][CH:12]([CH3:15])[N:13]3[C:14]=2[C:5]([C:3](=[O:4])[NH:22][C:23]3=[O:24])=[CH:6][C:7]=1[F:17]

Komponenten

6

Edukt 4

HCID 70918Chlorosulfonyl isocyanateHCID 517045Sodium AcetateHCID 210411905,6-Difluoro-2-methyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl esterHCID 23676156Sodium t-butoxide

Produkt 1

HCID 219790428,9-Difluoro-5-methyl-6,7-dihydro-5H-pyrido[3,2,1-ij]quinazoline-1,3-dioneAusbeute 72,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
-20 °C

Versuchsvorschrift

A solution of 1.07 g (4.4 mmol) of 5,6-difluoro-2-methyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester (Example 32) in 25 mL of dichloromethane is cooled to −20° C. and treated dropwise with 0.85 g (6.0 mmol) of chlorosulfonyl isocyanate. The reaction is stirred at −20° C. for 1 hour, treated with 1.0 g (12 mmol) of solid sodium acetate, and the solvent is removed in vacuo. The residue is cooled in an ice bath and triturated with a saturated solution of sodium acetate in brine. The precipitate is removed by filtration, washed with the sodium acetate solution and dried in vacuo. The dried precipitate is washed with ether to remove starting material and dried in vacuo. The dried solid is suspended in 40 mL of dry tetrahydrofuran, cooled to 5° C. and treated portionwise with 1.2 g (12 mmol) of sodium tert-butoxide. After the addition is complete, the reaction mixture is stirred at 5° C. for 30 minutes, the bath is removed, and the reaction is stirred to room temperature over 1 hour. The solvent is removed in vacuo; the residue is dissolved in water, cooled to 5° C. and acidified with formic acid. The resulting precipitate is removed by filtration, washed with water and dried in vacuo affording 0.8 g of the title compound, mp 212-214° C.

Aufarbeitung

  1. customthe solvent is removed in vacuo
  2. temperatureThe residue is cooled in an ice bath
  3. customtriturated with a saturated solution of sodium acetate in brine
  4. customThe precipitate is removed by filtration
  5. washwashed with the sodium acetate solution
  6. customdried in vacuo
  7. washThe dried precipitate is washed with ether
  8. customto remove
  9. customdried in vacuo
  10. temperaturecooled to 5° C.
  11. additionAfter the addition
  12. stirringthe reaction mixture is stirred at 5° C. for 30 minutes
  13. customthe bath is removed
  14. stirringthe reaction is stirred to room temperature over 1 hour
  15. customThe solvent is removed in vacuo
  16. dissolutionthe residue is dissolved in water
  17. temperaturecooled to 5° C.
  18. customThe resulting precipitate is removed by filtration
  19. washwashed with water
  20. customdried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-25aee4db792a4acca20f083d0fe2d7c3
Quelldatensatz
uspto-grants-2009_09
Patentnummer
US07582627B2

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