Piperazine → 6-Chloro-2-(piperazin-1-yl)-1,3-benzothiazole

HRID 33596

反応式

HRID 33596 の反応式
Cl[C:2]1[S:3][C:4]2[CH:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:5]=2[N:6]=1.C(=O)([O-])[O-].[K+].[K+].[NH:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1>CN(C=O)C>[Cl:11][C:9]1[CH:8]=[CH:7][C:5]2[N:6]=[C:2]([N:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)[S:3][C:4]=2[CH:10]=1

参加物

5

反応物 3

HCID 4837PiperazineHCID 11430Potassium CarbonateHCID 771762,6-Dichlorobenzothiazole

生成物 1

HCID 27465956-Chloro-2-(piperazin-1-yl)-1,3-benzothiazole収率 100%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a stirred solution of 1.07 g (5.24 mmol) of 2,6-dichlorobenzothiazole in dry DMF (25 mL) was added 2.4 g of potassium carbonate (15.7 mmol) and 0.5 g of piperazine (5.8 mmol). The mixture was stirred at room temperature for 4 h. When the reaction was complete it was partitioned between EtOAc (150 mL) and water (50 mL) and separated. The aqueous layer was extracted with EtOAC (2×100 mL). The combined organic layers were then washed with water (2×25 mL), brine, dried over Na2SO4, and the solvent was removed under reduced pressure to give 1.33 g (100%) of desired product as a white solid. MS (electrospray): exact mass calculated for C11H12ClN3S, 253.04; m/z found, 254.0 [M+H]+. B. 1-[1-{3-[4-(6-Chloro-benzothiazol-2-yl)-piperazin-1-yl]-2-hydroxy-propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone. To a stirred solution of 144 mg (0.39 mmol) of 1-[1-oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone in 4 mL of EtOH was added 100 mg (0.39 mmol) 6-chloro-2-piperazin-1-yl-benzothiazole. The solution was heated to 60° C. overnight. The solvent was then removed by rotary evaporation and the crude product was purified by column chromatography (silica, 0-10% MeOH/EtOAc) to afford 220 mg (90%) of a white solid. MS (electrospray): exact mass calculated for C29H30ClF3N6O2S: 618.18; m/z found, 619.2 [M+H]+. HPLC (reverse phase conditions 40-90%): tR=8.27 min. 1H NMR (CDCl3, 400 MHz, a mixture of amide rotamers): 7.70 (d, J=8.34 Hz, 1H), 7.62 (m, 2H), 7.57 (d, J=8.59 Hz, 1H), 7.48 (d, J=2.53 Hz, 1H), 7.36 (d, J=8.59 Hz, 1H), 7.16 (dd, J=8.59, 2.53 Hz, 1H), 4.80 and 4.68 (A and B of AB quartet, J=15.92 Hz, 1H), 4.58 (s, 1H), 4.18-4.08 (m, 2H), 4.01-3.89 (m, 2H), 3.85-3.60 (m, 2H), 3.59-3.47 (m, 4H), 2.94-2.75 (m, 2H), 2.72-2.62 (m, 2H), 2.55-2.47 (m, 2H), 2.46-2.39 (m, 2H), 2.13 (s, 1.5H), 2.08 (s, 1.5H).

後処理

  1. customwas partitioned between EtOAc (150 mL) and water (50 mL)
  2. customseparated
  3. extractionThe aqueous layer was extracted with EtOAC (2×100 mL)
  4. washThe combined organic layers were then washed with water (2×25 mL), brine
  5. dry with materialdried over Na2SO4
  6. customthe solvent was removed under reduced pressure

出典と根拠

ORDレコード
ord-8c72d178a5f24329b38417a37264240a
出典データセット
uspto-grants-2008_09
特許番号
US07429591B2

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