Water → 1-(4-methoxybenzyl)-5-phenyl-4-(piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine

HRID 387543Notes

Reaction equation

HRID 387543 reaction equation
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:9]=2[N:11]2[CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13][CH2:12]2)[N:4]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=2)[N:3]=1.C[NH:40]CCNC.C(=O)(OC(C)(C)C)N.O>O1CCOCC1.[Cu]I.C(OCC)(=O)C>[CH3:38][O:37][C:34]1[CH:33]=[CH:32][C:31]([CH2:30][N:4]2[C:5]3=[N:6][CH:7]=[C:8]([C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)[C:9]([N:11]4[CH2:12][CH2:13][NH:14][CH2:15][CH2:16]4)=[C:10]3[C:2]([NH2:40])=[N:3]2)=[CH:36][CH:35]=1

Participants

8

Reactant 4

HCID 962WaterHCID 8070N,N'-DimethylethylenediamineHCID 77922tert-Butyl carbamateHCID 68760648tert-butyl 4-(3-iodo-1-(4-methoxybenzyl)-5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate

Product 1

HCID 687585391-(4-methoxybenzyl)-5-phenyl-4-(piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridin-3-amineYield 97.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of tert-butyl 4-(3-iodo-1-(4-methoxybenzyl)-5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (1.55 g, 2.4780 mmol, see Example 9), CuI (0.47 g, 2.48 mmol), N1,N2-dimethylethane-1,2-diamine (0.53 ml, 4.96 mmol) and tert-butyl carbamate (2.90 g, 24.78 mmol) in dioxane (50 mL) was stirred at 75° C. (oil bath) for 6 hours. Water (50 mL) and ethyl acetate (50 mL) were added, and the organic layer was separated, washed with saturated ammonium chloride, dried (sodium sulfate) and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (hexane:ethyl acetate=1:1) to give 1-(4-methoxybenzyl)-5-phenyl-4-(piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine (1.00 g, 97%) as a solid. This solid was dissolved in DCM (20 mL), and TFA (4.77 mL, 62.0 mmol) was added. The reaction was stirred at room temperature for 4 hours. The solvent was removed. The residue was partitioned between saturated NaHCO3 (30 mL) and DCM (40 mL). The organic layer was separated, dried (sodium sulfate) and concentrated in vacuo to give 1-(4-methoxybenzyl)-5-phenyl-4-(piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine (1.00 g, 97%) as a solid. LCMS (APCI+) m/z 415(M+H)+.

Workup

  1. customthe organic layer was separated
  2. washwashed with saturated ammonium chloride
  3. dry with materialdried (sodium sulfate)
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography on silica gel (hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-0a8665e084f9484fb4bc57fdc417c55c
Source dataset
uspto-grants-2013_02
Patent number
US08372842B2

Reaction notes

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