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

HRID 387543노트

반응식

HRID 387543 반응식
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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

반응 조건

온도
75 °C

실험 절차

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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-0a8665e084f9484fb4bc57fdc417c55c
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08372842B2

반응 노트

불러오는 중…