1-Acetylpiperazine → 1-[4-(2-Chloro-3-methyl-pyridin-4-ylmethyl)-piperazin-1-yl]-ethanone

HRID 1355523Notes

Reaction equation

HRID 1355523 reaction equation
[Cl:1][C:2]1[C:7]([CH3:8])=[C:6]([CH2:9]Cl)[CH:5]=[CH:4][N:3]=1.[C:11]([N:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1)(=[O:13])[CH3:12]>CS(C)=O>[Cl:1][C:2]1[C:7]([CH3:8])=[C:6]([CH2:9][N:17]2[CH2:18][CH2:19][N:14]([C:11](=[O:13])[CH3:12])[CH2:15][CH2:16]2)[CH:5]=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 837951-AcetylpiperazineHCID 185068432-Chloro-4-(chloromethyl)-3-methylpyridine

Product 1

HCID 185068191-[4-(2-Chloro-3-methyl-pyridin-4-ylmethyl)-piperazin-1-yl]-ethanone

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

(2-Chloro-3-methyl-pyridin-4-yl)-methanol (12-4, impure, 0.200 g) was dissolved in 5 mL anhydrous DCM under N2. Anhydrous DMF (0.098 mL, 1.3 mmol) and POCl3 (0.118 mL, 1.27 mmol) were added and the reaction was stirred at RT for 17 h. The reaction was quenched with sat NaHCO3 (aq) and extracted 3× with DCM. The organic phases were dried over Na2SO4, filtered and concentrated to provide 2-chloro-4-chloromethyl-3-methyl-pyridine still contaminated with a major by-product. 2-Chloro-4-chloromethyl-3-methyl-pyridine (impure, 0.215 g) was stirred in 3 mL DMSO. 1-Acetylpiperazine (0.626 g, 4.88 mmol was added and the reaction was stirred at RT overnight. The solution was purified by directly loading onto a preparative reverse phase column to afford an oil which slowly crystallizes. TFA salt: 1H NMR (CD3OD) δ 8.30 (d, 1H, J=5.0 Hz), 7.53 (d, 1H, J=5.0 Hz), 4.48 (s, 2H), 3.84 (bs, 4H), 3.39-3.30 (m, 4H), 2.14 (s, 3H).

Workup

  1. customThe solution was purified
  2. customto afford an oil which
  3. customslowly crystallizes

Sources & evidence

ORD record
ord-b74347a309214c9885582d5c89e8df50
Source dataset
uspto-grants-2003_07
Patent number
US06586424B2

Reaction notes

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