4-Toluenesulfonyl chloride → 3-Cyclopropyl-1-(2-fluoro-4-iodophenyl)-6,8-dimethyl-5-(((4-methylphenyl)sulfonyl)oxy)pyrido(2,3-d)pyrimidine-2,4,7(1H,3H,8H)-trione

HRID 2224172Notes

Reaction equation

HRID 2224172 reaction equation
[CH:1]1([N:4]2[C:9](=[O:10])[C:8]3[C:11]([OH:18])=[C:12]([CH3:17])[C:13](=[O:16])[N:14]([CH3:15])[C:7]=3[N:6]([C:19]3[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=3[F:26])[C:5]2=[O:27])[CH2:3][CH2:2]1.C(N(CC)CC)C.Cl.CN(C)C.[S:40](Cl)([C:43]1[CH:49]=[CH:48][C:46]([CH3:47])=[CH:45][CH:44]=1)(=[O:42])=[O:41]>C(#N)C.CO>[CH:1]1([N:4]2[C:9](=[O:10])[C:8]3[C:11]([O:18][S:40]([C:43]4[CH:49]=[CH:48][C:46]([CH3:47])=[CH:45][CH:44]=4)(=[O:42])=[O:41])=[C:12]([CH3:17])[C:13](=[O:16])[N:14]([CH3:15])[C:7]=3[N:6]([C:19]3[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=3[F:26])[C:5]2=[O:27])[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 10313079Trimethylamine HydrochlorideHCID 597170043-Cyclopropyl-1-(2-fluoro-4-iodophenyl)-5-hydroxy-6,8-dimethylpyrido(2,3-d)pyrimidine-2,4,7(1H,3H,8H)-trione

Product 1

HCID 597170443-Cyclopropyl-1-(2-fluoro-4-iodophenyl)-6,8-dimethyl-5-(((4-methylphenyl)sulfonyl)oxy)pyrido(2,3-d)pyrimidine-2,4,7(1H,3H,8H)-trioneYield 91%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent2×

Procedure

Under a nitrogen atmosphere, to 3-cyclopropyl-1-(2-fluoro-4-iodo-phenyl)-5-hydroxy-6,8-dimethyl-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione 55 (23.9 g) was added acetonitrile (167 ml), and the mixture was stirred under ice-cooling. Triethylamine (11.0 ml) and trimethylamine hydrochloride (2.37 g) were added, and a solution of p-toluenesulfonyl chloride 11 (12.3 g) in acetonitrile (72.0 ml) was added dropwise. The mixture was stirred under ice-cooling for 1 hr, and stirred at room temperature for 3 hrs. Methanol (239 ml) was added, and the mixture was stirred at room temperature for 1 hr. The crystals were collected by filtration and dried to give p-toluenesulfonic acid 3-cyclopropyl-1-(2-fluoro-4-iodo-phenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-yl ester 77 (28.7 g, yield 91%) as colorless crystals.

Workup

  1. temperaturecooling
  2. stirringThe mixture was stirred under ice-
  3. temperaturecooling for 1 hr
  4. stirringstirred at room temperature for 3 hrs
  5. stirringthe mixture was stirred at room temperature for 1 hr
  6. filtrationThe crystals were collected by filtration
  7. customdried

Sources & evidence

ORD record
ord-a947e657e5864e28a80b8073c347ff3a
Source dataset
uspto-grants-2008_05
Patent number
US07378423B2

Reaction notes

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