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Trifluoroacetic acid → N-[3-chloro-2-(4-{2-hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo [4,3-c]pyridin-1-yl]-propyl}-piperazin-1-yl)-phenyl]-methanesulfonamide

HRID 2055808
ノート
印刷プレビュー

反応式

HRID 2055808 の反応式
C(O[C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([NH:20][S:21]([CH3:24])(=[O:23])=[O:22])=[CH:18][CH:17]=[CH:16][C:15]=2[Cl:25])[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.[CH3:33][S:34]([N:37]1[CH2:42][CH2:41][C:40]2[N:43]([CH2:56][CH:57]3C[O:58]3)[N:44]=[C:45]([C:46]3[CH:51]=[CH:50][C:49]([C:52]([F:55])([F:54])[F:53])=[CH:48][CH:47]=3)[C:39]=2[CH2:38]1)(=[O:36])=[O:35]>C(Cl)Cl>[Cl:25][C:15]1[C:14]([N:11]2[CH2:10][CH2:9][N:8]([CH2:6][CH:57]([OH:58])[CH2:56][N:43]3[C:40]4[CH2:41][CH2:42][N:37]([S:34]([CH3:33])(=[O:36])=[O:35])[CH2:38][C:39]=4[C:45]([C:46]4[CH:51]=[CH:50][C:49]([C:52]([F:54])([F:55])[F:53])=[CH:48][CH:47]=4)=[N:44]3)[CH2:13][CH2:12]2)=[C:19]([NH:20][S:21]([CH3:24])(=[O:22])=[O:23])[CH:18]=[CH:17][CH:16]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 6422Trifluoroacetic acidHCID 120720315-methanesulfonyl-1-oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridineHCID 684630944-(2-Chloro-6-methanesulfonylamino-phenyl)-piperazine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 10168894N-[3-chloro-2-(4-{2-hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo [4,3-c]pyridin-1-yl]-propyl}-piperazin-1-yl)-phenyl]-methanesulfonamide
収率 83.2%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
25 °C

実験手順

4-(2-Chloro-6-methanesulfonylamino-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (145 mg, 0.37 mmol) was dissolved in 3 mL of CH2Cl2 and treated with 1.5 mL of trifluoroacetic acid. The reaction mixture was stirred at 25° C. for 1 h before all volatiles were removed. The solid was treated with CH2Cl2 (20 mL) and aqueous KOH (4 N, 10 mL). The organic layer was separated, dried over Na2SO4, and concentrated. The crude oil (90 mg) was dissolved in absolute EtOH (1.0 mL) and treated with 96 mg (0.24 mmol) of 5-methanesulfonyl-1-oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine. The reaction mixture was refluxed at 85° C. for 3 h and then the solvent was removed. Column chromatography (silica, 0-5% MeOH/CH2Cl2) provided 138 mg (20% over 4 steps) of N-[3-chloro-2-(4-{2-hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperazin-1-yl)-phenyl]-methanesulfonamide. TLC (silica, 5% MeOH/CH2Cl2): Rf=0.45. MS (electrospray): exact mass calculated for C28H34CIF3N6O5S2, 690.17; m/z found, 691.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.28 (s, 1H), 7.65 and 7.59 (AB pattern, J=8.4 Hz, 4H), 7.36 (d, J=8.1 Hz, 1H), 7.07 (t, J=8.2 Hz, 1H), 6.9 (d, J=8.2 Hz, 1H), 4.54-4.44 (m, 2H), 4.21-3.94 (m, 3H), 3.77-3.52 (m, 4H), 3.41 (m, 2H), 2.96 (s, 3H), 2.81 (s, 3H), 3.05-2.73 (m, 4H), 2.66-2.20 (m, 4H).

後処理

  1. customwere removed
  2. additionThe solid was treated with CH2Cl2 (20 mL) and aqueous KOH (4 N, 10 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. dissolutionThe crude oil (90 mg) was dissolved in absolute EtOH (1.0 mL)
  7. temperatureThe reaction mixture was refluxed at 85° C. for 3 h
  8. customthe solvent was removed

出典と根拠

ORDレコード
ord-2798019302fb46808562b0c3c98d2a1b
出典データセット
uspto-grants-2008_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07332494B2

反応ノート

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