Amantadine → 4H-Pyrido(1,2-a)pyrimidine-3-carboxamide, 6-methyl-4-oxo-N-tricyclo(3.3.1.1(sup 3,7))dec-1-yl-

HRID 1655924Notes

Reaction equation

HRID 1655924 reaction equation
[CH3:1][C:2]1[N:7]2[C:8](=[O:15])[C:9]([C:12]([OH:14])=O)=[CH:10][N:11]=[C:6]2[CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.ClC(OC)=O.[C:28]12([NH2:38])[CH2:37][CH:32]3[CH2:33][CH:34]([CH2:36][CH:30]([CH2:31]3)[CH2:29]1)[CH2:35]2>C(Cl)(Cl)Cl>[C:28]12([NH:38][C:12]([C:9]3[C:8](=[O:15])[N:7]4[C:2]([CH3:1])=[CH:3][CH:4]=[CH:5][C:6]4=[N:11][CH:10]=3)=[O:14])[CH2:35][CH:34]3[CH2:33][CH:32]([CH2:31][CH:30]([CH2:36]3)[CH2:29]1)[CH2:37]2

Participants

6

Reactant 4

HCID 2130AmantadineHCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 2084164H-Pyrido(1,2-a)pyrimidine-3-carboxylic acid, 6-methyl-4-oxo-

Product 1

HCID 30792964H-Pyrido(1,2-a)pyrimidine-3-carboxamide, 6-methyl-4-oxo-N-tricyclo(3.3.1.1(sup 3,7))dec-1-yl-Yield 65.2%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent3×

Procedure

A mixture containing 4.08 (0.02 mole) of 6-methyl-4-oxo-4H-pyrido[1.2-a]pyrimidine-3-carboxylic acid and 3.1 ml (0.022 mol) of triethylamine in 120 ml of chloroform is cooled below -10° C. by ice-salt. A solution of 2.52 ml (0.026 mol) of methyl chloroformate in 10 ml of chloroform is dropped to the above mixture at -15° C. during 10 minutes. After stirring for 5 minutes, 3.33 g (0.022 mol) of 1-adamantanamine dissolved in 20 ml of chloroform are dropped to the above solution at -15 0° C. during 15 minutes. The reaction mixture is stirred below -10° C. for 1 hour, then allowed to stand overnight under cooling by ice. For working up, the reaction mixture is washed 3 times with 70 ml of 5% sodium hydrogen carbonate solution each, then 3 times with 70 ml of water each. The organic phase is dried over anhydrous sodium sulfate, filtered and evaporated to yield 4.4 g (65.2%) of the named product as pale yellow crystals after recrystallization from ethanol, m.p.: 190°-193° C.

Workup

  1. additionare dropped to the above solution at -15 0° C. during 15 minutes
  2. stirringThe reaction mixture is stirred below -10° C. for 1 hour
  3. waitto stand overnight
  4. temperatureunder cooling by ice
  5. washthe reaction mixture is washed 3 times with 70 ml of 5% sodium hydrogen carbonate solution each, then 3 times with 70 ml of water each
  6. dry with materialThe organic phase is dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-22aa262dbdc4463e820ab4e8c1199918
Source dataset
uspto-grants-1993_10
Patent number
US05252572

Reaction notes

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