Acetamidine monohydrochloride → t-butyl 2-methyl-4-(trifluoromethyl)-5,8-dihydropyrido[3,4-d]pyrimidin-7(6H)-carboxylate

HRID 1360179Notes

Reaction equation

HRID 1360179 reaction equation
[O-]CC.[Na+].Cl.[C:6]([NH2:9])(=[NH:8])[CH3:7].O=[C:11]1[CH:16]([C:17](=O)[C:18]([F:21])([F:20])[F:19])[CH2:15][CH2:14][N:13]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:12]1>C(O)C>[CH3:7][C:6]1[N:8]=[C:17]([C:18]([F:21])([F:20])[F:19])[C:16]2[CH2:15][CH2:14][N:13]([C:23]([O:25][C:26]([CH3:29])([CH3:27])[CH3:28])=[O:24])[CH2:12][C:11]=2[N:9]=1

Participants

5

Reactant 3

HCID 67170Acetamidine monohydrochlorideHCID 2723922Sodium ethoxideHCID 18456551tert-Butyl 3-oxo-4-(2,2,2-trifluoroacetyl)piperidine-1-carboxylate

Product 1

HCID 66969237t-butyl 2-methyl-4-(trifluoromethyl)-5,8-dihydropyrido[3,4-d]pyrimidin-7(6H)-carboxylateYield 16%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
80 °C

Procedure

1.3 mL of sodiumethoxide (21% wt. ethanol solution) was added at room temperature to a solution in which 283 mg (3.0 mmol) of acetamidine hydrochloric acid salt was dissolved in 5 mL of absolute ethanol. After stirring of 15 minutes, to the resulting solution, was added a solution in which 590 mg (2.0 mmol) of t-butyl 3-oxo-4-(trifluoroacetyl)-piperidin-1-carboxylate obtained in PREPARATION 47 was diluted with 5 mL of absolute ethanol. The resulting mixture was heated to 80° C. and stirred for 18 hours. After cooling to room temperature, ethanol was distilled off under reduced pressure, followed by washing with saline which was diluted with ethylacetate. An organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure and then the residue was purified by column chromatography (10:1 hexane:ethyl acetate) to give 98 mg of the title compound in a yield of 16%.

Workup

  1. customobtained in PREPARATION 47
  2. stirringstirred for 18 hours
  3. temperatureAfter cooling to room temperature
  4. distillationethanol was distilled off under reduced pressure
  5. washby washing with saline which
  6. additionwas diluted with ethylacetate
  7. dry with materialAn organic layer was dried over anhydrous magnesium sulfate
  8. distillationthe solvent was distilled off under reduced pressure
  9. customthe residue was purified by column chromatography (10:1 hexane:ethyl acetate)

Sources & evidence

ORD record
ord-b01232320288410dad5db383e37a7f15
Source dataset
uspto-grants-2011_02
Patent number
US07879848B2

Reaction notes

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