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 79589노트

반응식

HRID 79589 반응식
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]

참가 물질

6

반응물 4

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

생성물 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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-06ccb4d1cbdb4ceda77e019a5f8a5bed
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08841304B2

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