Hydrochloric Acid → HCID 68818290、化合物

HRID 734357

反応式

HRID 734357 の反応式
[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].C1(C2C=C(F)[CH:24]=[CH:23][C:22]=2[C:28]([C:30]2[CH:35]=[CH:34][C:33](F)=[CH:32][C:31]=2C2CC2)=[O:29])CC1.C(=O)([O-])[O-].[K+].[K+].[ClH:46]>CS(C)=O.CO.C(OCC)C>[ClH:46].[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([CH:12]2[CH2:13][CH2:14][N:15]([C:33]3[CH:32]=[CH:31][C:30]([C:28]([CH:22]4[CH2:23][CH2:24]4)=[O:29])=[CH:35][CH:34]=3)[CH2:16][CH2:17]2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2]

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 28282195HCID 28282195、化合物HCID 53737258Cyclopropyl-4-fluorophenyl ketone

生成物 1

HCID 68818290HCID 68818290、化合物

試薬・触媒・溶媒 3

HCID 679Dimethyl Sulfoxide溶媒HCID 887Methanol溶媒HCID 3283Diethyl Ether溶媒

反応条件

温度
140 °C

実験手順

To 1-isopropyl-4-(piperidine-4-carbonyl)-piperazine (D1)(0.25 g) and cyclopropyl-4-fluorophenyl ketone (0.3 g), dissolved in DMSO (5 ml) was added potassium carbonate (0.37 g). The reaction was heated to 140° C. for 2 h. After cooling the mixture, the inorganics were filtered off. The filtrate was diluted with MeOH (20 ml) and then poured onto a 10 g isolute SCX column which was washed with MeOH (50 ml). The product was eluted with 10% ammonia in MeOH (50 ml), and then further purified by column chromatography [silica gel, step gradient 0-10% MeOH (containing 10% 0.88 ammonia solution) in DCM]. Fractions containing the required product were evaporated to give the free base which was dissolved in MeOH (4 ml) and treated with 1N HCl in diethyl ether (2 ml) to give the title compound (E105) as a solid (51mg). 1H NMR δ [DMSO-d6]: 0.93 (4H, m) 1.27 (6H, d, J=6.4 Hz), 1.5-1.8 (2H, m), 2.77-3.14 (7H, m), 3.38-3.48 (2H, m), 3.92-4.56 (4H, m), 6.98 (2H, d, J=9.2 Hz), 7.89 (2H, d, J=9.2 Hz), 10.6 (1H, br s). MS electrospray; (+ve ion) 384 (MH+).

後処理

  1. temperatureAfter cooling the mixture
  2. filtrationthe inorganics were filtered off
  3. additionThe filtrate was diluted with MeOH (20 ml)
  4. additionpoured onto a 10 g isolute SCX column which
  5. washwas washed with MeOH (50 ml)
  6. washThe product was eluted with 10% ammonia in MeOH (50 ml)
  7. customfurther purified by column chromatography [silica gel, step gradient 0-10% MeOH (containing 10% 0.88 ammonia solution) in DCM]
  8. additionFractions containing the required product
  9. customwere evaporated
  10. customto give the free base which

出典と根拠

ORDレコード
ord-fc9e64f6dc854addb070e413361ddf48
出典データセット
uspto-grants-2009_09
特許番号
US07592347B2

関連ノート

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