3-(Chloromethyl)pyridine hydrochloride → HCID 14775274, compound

HRID 1535088Notes

Reaction equation

HRID 1535088 reaction equation
[H-].[Na+].[CH2:3]([C:7]1[C:8]2[N:9]([C:19]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])=[N:20][N:21]=2)[CH:10]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:12]=1)[CH:4]([CH3:6])[CH3:5].[H][H].Cl.Cl[CH2:32][C:33]1[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=1>CN(C=O)C>[CH2:3]([C:7]1[C:8]2[N:9]([C:19]([CH:22]([CH2:32][C:33]3[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=3)[C:23]([O:25][CH2:26][CH3:27])=[O:24])=[N:20][N:21]=2)[CH:10]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:12]=1)[CH:4]([CH3:6])[CH3:5]

Participants

6

Reactant 4

HCID 233943-(Chloromethyl)pyridine hydrochlorideHCID 24758Sodium hydrideHCID 14775265HCID 14775265, compoundHCID 178418361HCID 178418361, compound2×

Product 1

HCID 14775274HCID 14775274, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

Sodium hydride (202 mg) was added to a solution of ethyl 8-isobutyl-6-phenyl-1,2,4-triazolo[4,3-a]pyrazin-3-ylacetate (1.35 g) in DMF (10 ml) with stirring at 0° C. under an atmosphere of argon. When evolution of hydrogen had ceased (approximately 15 minutes), a solution of 3-chloromethylpyridine hydrochloride (722 mg) in DMF (5 ml) was added dropwise over 5 minutes. The mixture was stirred at 0° C. until hydrogen evolution ceased and then at ambient temperature for 2 hours. The mixture was added to ice-cold 0.5 M hydrochloric acid (60 ml). The solution was washed with ether (50 ml) and then basified by addition of solid sodium hydrogen carbonate. The resulting emulsion was extracted with ethyl acetate (2×50 ml). The combined extracts were washed with water (50 ml), followed by saturated sodium chloride solution (50 ml) and dried (MgSO4). The solvent was removed by evaporation and the residue was purified by flash chromatography, eluting with methanol/dichloromethane (3:97 v/v), to give ethyl 2-[8-isobutyl-6-phenyl-1,2,4-triazolo[4,3-a]pyrazin-3-yl]-3-(3-pyridyl)propionate (B), as a white powder (1.1 g), m.p. 110°-111° (after trituration with ether); NMR (CDCl3): 1.1 (d, 6H), 1.2 (t, 3H), 2.6 (m, 1H), 3.3 (d, 2H), 3.75 (ddd, 2H), 4.2 (q, 2H), 4.5 (t, 1H), 7.2 (dd, 1H), 7.5 (m,3H), 7.6 (m, 1H), 7.9 (m, 2H), 7.9 (dd, 1H), 8.2 (s, 1H), 8.4 (dd, 1H), 8.6 (d, 1H).

Workup

  1. custom(approximately 15 minutes)
  2. washThe solution was washed with ether (50 ml)
  3. additionbasified by addition of solid sodium hydrogen carbonate
  4. extractionThe resulting emulsion was extracted with ethyl acetate (2×50 ml)
  5. washThe combined extracts were washed with water (50 ml)
  6. dry with materialdried (MgSO4)
  7. customThe solvent was removed by evaporation
  8. customthe residue was purified by flash chromatography
  9. washeluting with methanol/dichloromethane (3:97 v/v)

Sources & evidence

ORD record
ord-80eae4583ff04b25847a921bf362db73
Source dataset
uspto-grants-1992_02
Patent number
US05091425

Reaction notes

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