Triethylamine → 8-(Cyclopropylmethoxy)-2-(methylthio)pyrido[3,4-d]pyrimidine

HRID 1480822Notes

Reaction equation

HRID 1480822 reaction equation
[CH3:1][S:2][C:3]1[N:4]=[CH:5][C:6]2[CH:12]=[CH:11][NH:10][C:9](=[O:13])[C:7]=2[N:8]=1.Br[CH2:15][CH:16]1[CH2:18][CH2:17]1.CCN(CC)CC>C(Cl)(Cl)Cl.C(=O)([O-])[O-].[Ag+2]>[CH:16]1([CH2:15][O:13][C:9]2[C:7]3[N:8]=[C:3]([S:2][CH3:1])[N:4]=[CH:5][C:6]=3[CH:12]=[CH:11][N:10]=2)[CH2:18][CH2:17]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 81503Bromomethylcyclopropane3×HCID 899959692-(Methylthio)pyrido[3,4-d]pyrimidin-8(7H)-one

Product 1

HCID 899961898-(Cyclopropylmethoxy)-2-(methylthio)pyrido[3,4-d]pyrimidineYield 17.4%

Reagents, catalysts & solvents 2

HCID 178418647HCID 178418647, compoundCatalystHCID 6212ChloroformSolvent

Procedure

A suspension of 2-(methylthio)pyrido[3,4-d]pyrimidin-8(7H)-one (Preparation 32, 502 mg, 2.60 mmol) and silver carbonate (988 mg, 3.58 mmol) in CHCl3 (25 mL) was treated with bromomethyl cyclopropane (310 μl, 3.19 mmol) and stirred at room temperature for 18 hours. The mixture was stirred at reflux for 4 hours and additional bromomethyl cyclopropane (310 μl, 3.19 mmol) was added. The reaction was stirred for 18 hours at 6° C. Further bromomethyl cyclopropane (310 μl, 3.19 mmol) was added and heated continued for 2 hours. Et3N was added (6 mL), the mixture filtered through celite washing with DCM and the solvent removed under reduced pressure. The residue was purified by silica gel column chromatography eluting with 0 to 80% EtOAc in cyclohexane to give the title compound (112 mg, 17%).

Workup

  1. stirringThe mixture was stirred
  2. temperatureat reflux for 4 hours
  3. stirringThe reaction was stirred for 18 hours at 6° C
  4. temperatureheated
  5. waitcontinued for 2 hours
  6. filtrationthe mixture filtered
  7. washthrough celite washing with DCM
  8. customthe solvent removed under reduced pressure
  9. customThe residue was purified by silica gel column chromatography
  10. washeluting with 0 to 80% EtOAc in cyclohexane

Sources & evidence

ORD record
ord-98c9f6e6ae2f495f95c5f791100a12ef
Source dataset
uspto-grants-2016_08
Patent number
US09409907B2

Reaction notes

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