Diisopropylethylamine → (S)-tert-butyl 5-((S)-1-(4-chlorophenyl)-2-oxo-2-(4-(5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)ethyl)-2,2-dimethylpyrrolidine-1-carboxylate

HRID 387574Notes

Reaction equation

HRID 387574 reaction equation
CCN(C(C)C)C(C)C.Cl.Cl.[C:12]1([C:18]2[C:19]([N:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)=[C:20]3[CH:26]=[N:25][NH:24][C:21]3=[N:22][CH:23]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[C:33]([O:37][C:38]([N:40]1[C:44]([CH3:46])([CH3:45])[CH2:43][CH2:42][C@H:41]1[C@H:47]([C:51]1[CH:56]=[CH:55][C:54]([Cl:57])=[CH:53][CH:52]=1)[C:48](O)=[O:49])=[O:39])([CH3:36])([CH3:35])[CH3:34].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C(Cl)Cl>[Cl:57][C:54]1[CH:53]=[CH:52][C:51]([C@@H:47]([C@H:41]2[N:40]([C:38]([O:37][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:39])[C:44]([CH3:46])([CH3:45])[CH2:43][CH2:42]2)[C:48](=[O:49])[N:30]2[CH2:29][CH2:28][N:27]([C:19]3[C:18]([C:12]4[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=4)=[CH:23][N:22]=[C:21]4[NH:24][N:25]=[CH:26][C:20]=34)[CH2:32][CH2:31]2)=[CH:56][CH:55]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 59564936(S)-2-((S)-1-(tert-Butoxycarbonyl)-5,5-dimethylpyrrolidin-2-yl)-2-(4-chlorophenyl)acetic acidHCID 68756523HCID 68756523, compound

Product 1

HCID 68760117(S)-tert-butyl 5-((S)-1-(4-chlorophenyl)-2-oxo-2-(4-(5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)ethyl)-2,2-dimethylpyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

DIEA (0.0475 mL, 0.273 mmol) was added to a solution of 5-phenyl-4-(piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridine dihydrochloride (0.030 g, 0.0681 mmol, See Example 1), (S)-2-((S)-1-(tert-butoxycarbonyl)-5,5-dimethylpyrrolidin-2-yl)-2-(4-chlorophenyl)acetic acid (0.0251 g, 0.0681 mmol, see Example D) and TBTU (0.0263 g, 0.0818 mmol) in DCM (1 mL) and stirred at room temperature for 16 hours. The mixture was directly loaded onto a silica column and purified by chromatography (hexane:ethyl acetate, 1:1) to give (S)-tert-butyl 5-((S)-1-(4-chlorophenyl)-2-oxo-2-(4-(5-phenyl-1H-pyrazolo[3,4-b]pyridin-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 and then concentrated to dryness. The resulting residue was dissolved in DCM (0.5 mL), and HCl in ether (1 mL, 2N) was added. The resulting solid was collected by filtration to give (S)-2-(4-chlorophenyl)-2-((S)-5,5-dimethylpyrrolidin-2-yl)-1-(4-(5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)ethanone (0.019, 46%). MS APCI (+) m/z 529.3 detected.

Workup

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

Sources & evidence

ORD record
ord-b230730e16cc4672a632d75515f49677
Source dataset
uspto-grants-2013_02
Patent number
US08372842B2

Reaction notes

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