Diisopropylethylamine → (S)-tert-butyl 5-((S)-1-(4-chloro-3-fluorophenyl)-2-oxo-2-(4-(5-phenyl-1H-pyrrolo[2,3-b]pyri din-4-yl)piperazin-1-yl)ethyl)-2,2-dimethylpyrrolidine-1-carboxylate

HRID 79589ノート

反応式

HRID 79589 の反応式
Cl.Cl.[C:3]1([C:9]2[C:10]([N:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)=[C:11]3[CH:17]=[CH:16][NH:15][C:12]3=[N:13][CH:14]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Na+].[C:25]([O:29][C:30]([N:32]1[C:36]([CH3:38])([CH3:37])[CH2:35][CH2:34][C@H:33]1[C@H:39]([C:43]1[CH:48]=[CH:47][C:46]([Cl:49])=[C:45]([F:50])[CH:44]=1)[C:40]([O-])=[O:41])=[O:31])([CH3:28])([CH3:27])[CH3:26].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[Cl:49][C:46]1[CH:47]=[CH:48][C:43]([C@@H:39]([C@H:33]2[N:32]([C:30]([O:29][C:25]([CH3:27])([CH3:26])[CH3:28])=[O:31])[C:36]([CH3:38])([CH3:37])[CH2:35][CH2:34]2)[C:40](=[O:41])[N:21]2[CH2:20][CH2:19][N:18]([C:10]3[C:9]([C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=4)=[CH:14][N:13]=[C:12]4[NH:15][CH:16]=[CH:17][C:11]=34)[CH2:23][CH2:22]2)=[CH:44][C:45]=1[F:50]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 68734733HCID 68734733、化合物HCID 687587805-phenyl-4-(piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridine dihydrochloride

生成物 1

HCID 68761234(S)-tert-butyl 5-((S)-1-(4-chloro-3-fluorophenyl)-2-oxo-2-(4-(5-phenyl-1H-pyrrolo[2,3-b]pyri din-4-yl)piperazin-1-yl)ethyl)-2,2-dimethylpyrrolidine-1-carboxylate

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

5-Phenyl-4-(piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridine dihydrochloride (0.0200 g, 0.0570 mmol, see Example 19), (S)-2-((S)-1-(tert-butoxycarbonyl)-5,5-dimethylpyrrolidin-2-yl)-2-(4-chloro-3-fluorophenyl)acetic acid (0.020 g, 0.0518 mmol, see Example D) and TBTU (0.0200 g, 0.0622 mmol) in DCM (1 mL) were added to DIEA (0.0361 mL, 0.207 mmol) and stirred at room temperature for 1 hour. The mixture was directly loaded to column and purified by chromatography (1:1 hexane:ethyl acetate) to give (S)-tert-butyl 5-((S)-1-(4-chloro-3-fluorophenyl)-2-oxo-2-(4-(5-phenyl-1H-pyrrolo[2,3-b]pyri din-4-yl)piperazin-1-yl)ethyl)-2,2-dimethylpyrrolidine-1-carboxylate as a solid. The solid was dissolved in DCM (1 mL) and TFA (0.2 mL) was added. The mixture was stirred at room temperature for 1 hour. The solvent was removed. The resulting residue was dissolved in DCM (0.5 mL), and 2M HCl in ether (1 mL) was added. The resulting solid was collected by filtration to give (S)-2-(4-chloro-3-fluorophenyl)-2-((S)-5,5-dimethylpyrrolidin-2-yl)-1-(4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)ethanone dihydrochloride (0.009 g, 28%). MS APCI (+) m/z 546 detected.

後処理

  1. custompurified by chromatography (1:1 hexane:ethyl acetate)

出典と根拠

ORDレコード
ord-06ccb4d1cbdb4ceda77e019a5f8a5bed
出典データセット
uspto-grants-2014_09
特許番号
US08841304B2

反応ノート

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