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

HRID 1355523ノート

反応式

HRID 1355523 の反応式
[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

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

実験手順

(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).

後処理

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

出典と根拠

ORDレコード
ord-b74347a309214c9885582d5c89e8df50
出典データセット
uspto-grants-2003_07
特許番号
US06586424B2

反応ノート

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