6-bromo-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one → 6-bromo-8-(2-cyclopropyl-6-fluorobenzyl)-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one

HRID 1190931Notes

Reaction equation

HRID 1190931 reaction equation
[Br:1][C:2]1[C:13](=[O:14])[NH:12][C:5]2[N:6]=[C:7]([S:10][CH3:11])[N:8]=[CH:9][C:4]=2[CH:3]=1.Cl[CH2:16][C:17]1[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=1[CH:24]1[CH2:26][CH2:25]1>CN(C)C=O>[Br:1][C:2]1[C:13](=[O:14])[N:12]([CH2:16][C:17]2[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=2[CH:24]2[CH2:25][CH2:26]2)[C:5]2[N:6]=[C:7]([S:10][CH3:11])[N:8]=[CH:9][C:4]=2[CH:3]=1

Participants

4

Reactant 2

HCID 221347206-bromo-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-oneHCID 679971832-Chloromethyl-1-cyclopropyl-3-fluorobenzene

Product 1

HCID 679973076-bromo-8-(2-cyclopropyl-6-fluorobenzyl)-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-oneYield 54%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 6-bromo-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one (7, 2.12 g, 7.8 mmol) in anhydrous dimethylformamide (40 mL) sodium hydride (60% on mineral oil, 467 mg, 11.7 mmol) was added and the reaction was stirred at room temperature for 30 min. A solution of 2-chloromethyl-1-cyclopropyl-3-fluorobenzene (1.58 g, 8.6 mmol) in anhydrous dimethylformamide (10 mL) was added slowly and the reaction was stirred for 18 h. The mixture was poured onto ice water (250 g) and extracted with dichloromethane (3×80 mL). The combined organic layers were dried over magnesium sulfate, filtered and evaporated. The residue was triturated with n-hexane, the precipitated product was collected, washed with methanol, then diethyl ether. The crude product was recrystallized from ethyl acetate to give the title compound (1.31 g, 3.1 mmol, 54%) as a pale yellow solid. ESMS m/z 420 (M+H)+.

Workup

  1. stirringthe reaction was stirred for 18 h
  2. additionThe mixture was poured onto ice water (250 g)
  3. extractionextracted with dichloromethane (3×80 mL)
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was triturated with n-hexane
  8. customthe precipitated product was collected
  9. washwashed with methanol
  10. customThe crude product was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-0ea63d31bd77494bb44a74655d2d4a72
Source dataset
uspto-grants-2014_03
Patent number
US08680099B2

Reaction notes

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