Acetic Acid → N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}methanesulfonamide

HRID 2224158Notes

Reaction equation

HRID 2224158 reaction equation
C[O-].[Na+].O1CCCC1.[CH:9]1([N:12]2[C:17](=[O:18])[C:16]3[C:19]([NH:26][C:27]4[CH:28]=[C:29]([NH:33][S:34]([CH3:37])(=[O:36])=[O:35])[CH:30]=[CH:31][CH:32]=4)=[C:20]([CH3:25])[C:21](=[O:24])[N:22]([CH3:23])[C:15]=3[N:14]([C:38]3[CH:43]=[CH:42][C:41]([I:44])=[CH:40][C:39]=3[F:45])[C:13]2=[O:46])[CH2:11][CH2:10]1.C(O)(=O)C>CO>[CH:9]1([N:12]2[C:17](=[O:18])[C:16]3=[C:15]([NH:14][C:38]4[CH:43]=[CH:42][C:41]([I:44])=[CH:40][C:39]=4[F:45])[N:22]([CH3:23])[C:21](=[O:24])[C:20]([CH3:25])=[C:19]3[N:26]([C:27]3[CH:28]=[C:29]([NH:33][S:34]([CH3:37])(=[O:36])=[O:35])[CH:30]=[CH:31][CH:32]=3)[C:13]2=[O:46])[CH2:10][CH2:11]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 10942334Sodium MethoxideHCID 59717182N-{3-[3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-ylamino]phenyl}methanesulfonamide

Product 1

HCID 59717300N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}methanesulfonamideYield 93%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Under a nitrogen atmosphere, to a solution (18.5 g) of 28% sodium methoxide in methanol was added tetrahydrofuran (284 ml), N-{3-[3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-ylamino]phenyl}methanesulfonamide 45 (28.4 g) obtained in Step 1 was added, and the mixture was stirred at room temperature for 1 hr. Acetic acid (12.5 ml) was added, and the mixture was stirred at room temperature for 1 hr and concentrated under reduced pressure. A 9:1 mixed solvent (426 mL) of 1-butanol and water was added to the obtained solid, and the mixture was stirred with heating under reflux for 3 hrs. The mixture was allowed to return to room temperature and stirred overnight, and the crystals were collected by filtration and dried. A 9:1 mixed solvent (426 mL) of 1-butanol and water was added again to the obtained crystals, and the mixture was stirred with heating under reflux for 3 hrs. The mixture was allowed to return to room temperature and stirred overnight. The crystals were collected by filtration and washed with a 9:1 mixed solvent of methanol and water and dried to give N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}methanesulfonamide 46 (26.35 g, yield 93%) as white crystals.

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at room temperature for 1 hr
  3. concentrationconcentrated under reduced pressure
  4. additionA 9:1 mixed solvent (426 mL) of 1-butanol and water was added to the obtained solid
  5. stirringthe mixture was stirred
  6. temperaturewith heating
  7. temperatureunder reflux for 3 hrs
  8. customto return to room temperature
  9. stirringstirred overnight
  10. filtrationthe crystals were collected by filtration
  11. customdried
  12. additionA 9:1 mixed solvent (426 mL) of 1-butanol and water was added again to the obtained crystals
  13. stirringthe mixture was stirred
  14. temperaturewith heating
  15. temperatureunder reflux for 3 hrs
  16. customto return to room temperature
  17. stirringstirred overnight
  18. filtrationThe crystals were collected by filtration
  19. washwashed with a 9:1 mixed solvent of methanol and water
  20. customdried

Sources & evidence

ORD record
ord-780d1eb90d73469e85c931bc6f687650
Source dataset
uspto-grants-2008_05
Patent number
US07378423B2

Reaction notes

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