2-Amino-6-methylpyridine → 2-(chloromethyl)-6-methyl-4H-pyrido[1,2-a]pyrimidin-4-one

HRID 405952Notes

Reaction equation

HRID 405952 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[N:3]=1.[Cl:9][CH2:10][C:11](=O)[CH2:12][C:13](OCC)=[O:14]>>[Cl:9][CH2:10][C:11]1[N:1]=[C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[N:3]2[C:13](=[O:14])[CH:12]=1

Participants

3

Reactant 2

HCID 157652-Amino-6-methylpyridineHCID 69484Ethyl 4-chloroacetoacetate

Product 1

HCID 7763672-(chloromethyl)-6-methyl-4H-pyrido[1,2-a]pyrimidin-4-one

Conditions

Temperature
125 °C

Procedure

A mixture of 2-amino-6-methylpyridine (10.00 g, 92.47 mmol), ethyl 4-chloro-acetoacetate (16.24 mL, 120.2 mmol), and polyphosphoric acid (50.00 g) was stirred at 125° C. After 5.5 h, the mixture was removed from the heat. To the cooled mixture was added ice-water (200 mL) and neutralized with 2 N NaOH (400 mL) to pH 6-7. The resulting precipitate was collected by filtration, washed with water (˜400 mL), and dried to give 2-(chloromethyl)-6-methyl-4H-pyrido-[1,2-a]pyrimidin-4-one as a dark brown solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 7.68 (1 H, dd, J=9.0, 7.0 Hz), 7.40 (1 H, dd, J=9.0, 0.8 Hz), 6.93 (1 H, d, J=6.7 Hz), 6.36 (1 H, s), 4.58 (2 H, s), 2.93 (3 H, s); Mass Spectrum (ESI) m/e=208.9 (M+1).

Workup

  1. customthe mixture was removed from the heat
  2. additionTo the cooled mixture was added ice-water (200 mL)
  3. filtrationThe resulting precipitate was collected by filtration
  4. washwashed with water (˜400 mL)
  5. customdried

Sources & evidence

ORD record
ord-83ae8aa5ad874f72bbda710812fc9d5c
Source dataset
uspto-grants-2014_06
Patent number
US08754089B2

Reaction notes

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