2-Aminopyridine → 2-(chloromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one

HRID 1784469Notes

Reaction equation

HRID 1784469 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C([O:10][C:11](=O)[CH2:12][C:13]([CH2:15][Cl:16])=O)C>>[Cl:16][CH2:15][C:13]1[N:1]=[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]2[C:11](=[O:10])[CH:12]=1

Participants

3

Reactant 2

HCID 104392-AminopyridineHCID 69484Ethyl 4-chloroacetoacetate

Product 1

HCID 51550272-(chloromethyl)-4H-pyrido[1,2-a]pyrimidin-4-oneYield 99%

Conditions

Temperature
120 °C

Procedure

15 g (159.4 mmol) of 2-aminopyridine (10) was combined with approximately 80 g of polyphosphoric acid and heated to 120° C. to allow stirring. To the resulting solution was added slowly 30.5 mL (223.2 mmol) of ethyl-4-chloroacetoacetate and stirred at 120° C. under nitrogen for two hours. The hot reaction mixture was then poured over 1500 mL of ice water and stirred vigorously. The aqueous layer was separated and extracted with methylene chloride (6×, approximately 6 L). The combined organic layers were washed with saturated NaHCO3 and brine and dried over MgSO4 and activated carbon. The solvent was removed in vacuo yielding 30.7 g (157.7 mmol, 99%) of 2-(chloromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (11) as a white solid.

Workup

  1. stirringstirred at 120° C. under nitrogen for two hours
  2. stirringstirred vigorously
  3. customThe aqueous layer was separated
  4. extractionextracted with methylene chloride (6×, approximately 6 L)
  5. washThe combined organic layers were washed with saturated NaHCO3 and brine
  6. dry with materialdried over MgSO4 and activated carbon
  7. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-2853ad1b901c40ae80bafeada5c16e43
Source dataset
uspto-grants-2009_03
Patent number
US07504405B2

Reaction notes

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