Potassium Carbonate → 6-(2,4-Difluorophenoxy)-8-((s)-2-hydroxypropyl)-2-methylsulfanyl-8h-pyrido[2,3-d]pyrimidin-7-one

HRID 2353306Notes

Reaction equation

HRID 2353306 reaction equation
[OH:1][C@@H:2]([CH3:15])[CH2:3][NH:4][C:5]1[C:10]([CH:11]=O)=[CH:9][N:8]=[C:7]([S:13][CH3:14])[N:6]=1.C[O:17][C:18](=O)[CH2:19][O:20][C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=1[F:28].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[F:28][C:22]1[CH:23]=[C:24]([F:27])[CH:25]=[CH:26][C:21]=1[O:20][C:19]1[C:18](=[O:17])[N:4]([CH2:3][C@@H:2]([OH:1])[CH3:15])[C:5]2[N:6]=[C:7]([S:13][CH3:14])[N:8]=[CH:9][C:10]=2[CH:11]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 23434554Methyl 2-(2,4-difluorophenoxy)acetateHCID 596814334-((S)-2-hydroxy-propylamino)-2-methylsulfanyl-pyrimidine-5-carbaldehyde

Product 1

HCID 596814276-(2,4-Difluorophenoxy)-8-((s)-2-hydroxypropyl)-2-methylsulfanyl-8h-pyrido[2,3-d]pyrimidin-7-oneYield 108.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 4-((S)-2-hydroxy-propylamino)-2-methylsulfanyl-pyrimidine-5-carbaldehyde (16.5 g, 73 mmol) and (2,4-difluorophenoxy)acetic acid methyl ester (29.4 g, 145 mmol) in anhydrous dimethyl formamide (300 mL) was added potassium carbonate (30 g, 218 mmol). The reaction mixture was heated to 60° C. and after 18 hours, the reaction mixture was cooled and the dimethylformamide was distilled off under vacuum. Crude residue suspended in water (300 mL) and extracted with dichloromethane, washed with brine and dried over magnesium sulfate. Filtered and concentrated under vacuum to give 41 g crude material which was chromatographed on silica gel column eluding with 1% methanol in dichloromethane to give 30 g 6-(2,4-difluorophenoxy)-8-((S)-2-hydroxypropyl)-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one (mass spec M+1=274).

Workup

  1. temperaturethe reaction mixture was cooled
  2. distillationthe dimethylformamide was distilled off under vacuum
  3. extractionextracted with dichloromethane
  4. washwashed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationFiltered
  7. concentrationconcentrated under vacuum
  8. customto give 41 g crude material which
  9. customwas chromatographed on silica gel column eluding with 1% methanol in dichloromethane

Sources & evidence

ORD record
ord-ea3498be5f11456aa15b40254cb7d8c7
Source dataset
uspto-grants-2010_07
Patent number
US07750016B2

Reaction notes

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