Methanol → tert-butyl 4-(3-methoxy-1-(4-methoxybenzyl)-5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate

HRID 387582Notes

Reaction equation

HRID 387582 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:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[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.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.[CH3:53][OH:54].[F-].[K+]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH3:53][O:54][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:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[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

Participants

7

Reactant 4

HCID 887MethanolHCID 13181,10-PhenanthrolineHCID 522689Potassium FluorideHCID 68760648tert-butyl 4-(3-iodo-1-(4-methoxybenzyl)-5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate

Product 1

HCID 68759898tert-butyl 4-(3-methoxy-1-(4-methoxybenzyl)-5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylateYield 96.4%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

tert-Butyl 4-(3-iodo-1-(4-methoxybenzyl)-5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (0.12 g, 0.192 mmol), Cu(I)I (0.0365 g, 0.192 mmol), 1,10-phenanthroline (0.0346 g, 0.192 mmol), methanol (0.389 mL, 9.59 mmol) and KF on Al2O3 (40%; 0.195 g, 1.34 mmol) in toluene (4 mL) was stirred at 110° C. for 20 hours. The reaction was cooled to room temperature. Ethyl acetate (10 mL) was then added, and the reaction mixture was filtered through a pad of celite. The filtrate was concentrated to dryness. The resulting residue was purified by column chromatography (hexane:ethyl acetate, 1:1) to give tert-butyl 4-(3-methoxy-1-(4-methoxybenzyl)-5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (0.098 g, 96%) as a solid. MS APCI (+) m/z 530.4 detected. 1H NMR (400 Hz, DMSO-d6) δ 8.06 (s, 1H), 7.46 (m, 2H), 7.33 (m, 3H), 7.20 (d, J=8.8 Hz, 2H), 6.87 (d, J=8.8 Hz, 2H), 5.38 (s, 2H), 3.98 (s, 3H), 3.71 (s, 3H), 3.29 (m, 4H), 2.94 (m, 4H), 1.37 (s, 9H).

Workup

  1. filtrationthe reaction mixture was filtered through a pad of celite
  2. concentrationThe filtrate was concentrated to dryness
  3. customThe resulting residue was purified by column chromatography (hexane:ethyl acetate, 1:1)

Sources & evidence

ORD record
ord-3c339a630c9d46b4aa8c06fc2470c523
Source dataset
uspto-grants-2013_02
Patent number
US08372842B2

Reaction notes

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