Sulfuric Acid → HCID 59128641, compound

HRID 1991009Notes

Reaction equation

HRID 1991009 reaction equation
[CH3:1][C:2](=[N:4][OH:5])[CH3:3].C([Li])CCC.CO[C:13](=O)[C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[C:16]([C:21]2[C:32](=[O:33])[N:31]([CH3:34])[C:24]3[N:25]=[C:26]([S:29][CH3:30])[N:27]=[CH:28][C:23]=3[CH:22]=2)[CH:15]=1.S(=O)(=O)(O)O.[OH-].[Na+]>C1COCC1>[CH3:34][N:31]1[C:24]2[N:25]=[C:26]([S:29][CH3:30])[N:27]=[CH:28][C:23]=2[CH:22]=[C:21]([C:16]2[CH:15]=[C:14]([C:13]3[O:5][N:4]=[C:2]([CH3:3])[CH:1]=3)[CH:19]=[CH:18][C:17]=2[CH3:20])[C:32]1=[O:33]

Participants

7

Reactant 5

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 67180Acetone, oximeHCID 59128631HCID 59128631, compoundHCID 178418339Butyllithium

Product 1

HCID 59128641HCID 59128641, compoundYield 3.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Propane-2-one oxime (62 mg, 0.844 mmol) was dissolved in 2 mL THF and cooled to 0° C. under nitrogen. n-Butyl lithium (0.68 mL of 2.5 M solution in hexanes, 1.688 mmol) was added slowly, so that the reaction temperature remained below 5° C. After stirring for 30 minutes, 4-methyl-3-(8-methyl-2-methylsulfanyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-6-yl)-benzoic acid methyl ester (200 mg, 0.56 mmol) was added, and the reaction mixture was stirred at 0° C. for one hour. Concentrated sulfuric acid (0.43 mL) was added dropwise, and the temperature was allowed to warm to room temperature over one hour. The reaction mixture was made pH neutral by addition of 1 M aqueous NaOH, and then partitioned between water and methylene chloride. The organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by preparative scale TLC plate, eluting with 25% EtOAc in hexanes then again with 0.25% MeOH in CH2Cl2, to give 8 mg of 8-methyl-6-[2-methyl-5-(3-methyl-isoxazol-5-yl)-phenyl]-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one; MS (M+H)=379.

Workup

  1. customremained below 5° C
  2. stirringthe reaction mixture was stirred at 0° C. for one hour
  3. temperatureto warm to room temperature over one hour
  4. custompartitioned between water and methylene chloride
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by preparative scale TLC plate
  9. washeluting with 25% EtOAc in hexanes

Sources & evidence

ORD record
ord-af4d4fdbe8ef4b13bfe6f021ea13c1d3
Source dataset
uspto-grants-2010_01
Patent number
US07645764B2

Reaction notes

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