Diisopropylethylamine → (S)-tert-butyl 2-(4-chlorophenyl)-3-(4-(5-(3-fluorophenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate

HRID 387562Notes

Reaction equation

HRID 387562 reaction equation
CCN(C(C)C)C(C)C.Cl.Cl.[F:12][C:13]1[CH:14]=[C:15]([C:19]2[C:20]([N:28]3[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]3)=[C:21]3[CH:27]=[N:26][NH:25][C:22]3=[N:23][CH:24]=2)[CH:16]=[CH:17][CH:18]=1.[C:34]([O:38][C:39]([N:41]([CH:54]([CH3:56])[CH3:55])[CH2:42][C@H:43]([C:47]1[CH:52]=[CH:51][C:50]([Cl:53])=[CH:49][CH:48]=1)[C:44](O)=[O:45])=[O:40])([CH3:37])([CH3:36])[CH3:35].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C(Cl)Cl>[Cl:53][C:50]1[CH:51]=[CH:52][C:47]([C@H:43]([C:44]([N:31]2[CH2:32][CH2:33][N:28]([C:20]3[C:19]([C:15]4[CH:16]=[CH:17][CH:18]=[C:13]([F:12])[CH:14]=4)=[CH:24][N:23]=[C:22]4[NH:25][N:26]=[CH:27][C:21]=34)[CH2:29][CH2:30]2)=[O:45])[CH2:42][N:41]([CH:54]([CH3:55])[CH3:56])[C:39](=[O:40])[O:38][C:34]([CH3:36])([CH3:35])[CH3:37])=[CH:48][CH:49]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 59564929(2S)-3-[tert-butoxycarbonyl(isopropyl)amino]-2-(4-chlorophenyl)propanoic acidHCID 687569845-(3-fluorophenyl)-4-(piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridine dihydrochloride

Product 1

HCID 68765028(S)-tert-butyl 2-(4-chlorophenyl)-3-(4-(5-(3-fluorophenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

DIEA (d 0.742; 0.0790 mL, 0.454 mmol) was added to a solution of 5-(3-fluorophenyl)-4-(piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridine dihydrochloride (0.070 g, 0.113 mmol), (S)-3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoic acid (0.0388 g, 0.113 mmol, see Example B) and TBTU (0.0437 g, 0.136 mmol) in DCM (1 mL) and stirred at room temperature for 18 hours. The mixture was directly loaded onto a silica column and purified by chromatography (hexane:ethyl acetate, 1:1) to give (S)-tert-butyl 2-(4-chlorophenyl)-3-(4-(5-(3-fluorophenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate 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)-1-(4-(5-(3-fluorophenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-3-(isopropylamino)propan-1-one dihydrochloride (0.022 g, 32%). MS APCI (+) m/z 521.4 detected.

Workup

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

Sources & evidence

ORD record
ord-5cb4e6fe1e834386bdaa9356c0546024
Source dataset
uspto-grants-2013_02
Patent number
US08372842B2

Reaction notes

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