Potassium Carbonate → 4-(4-amino-2-fluorophenoxy)-1-(4-methoxybenzyl)-N-(1-methylpiperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine

HRID 2241334Notes

Reaction equation

HRID 2241334 reaction equation
[CH3:1][O:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH2:24])=[CH:20][C:19]=4[F:25])=[C:11]3[C:10](I)=[N:9]2)=[CH:5][CH:4]=1.[CH3:29][N:30]1[CH2:35][CH2:34][CH:33]([NH2:36])[CH2:32][CH2:31]1.N1CCC[C@H]1C(O)=O.C([O-])([O-])=O.[K+].[K+]>CS(C)=O.[Cu]I.C(Cl)Cl>[NH2:24][C:21]1[CH:22]=[CH:23][C:18]([O:17][C:16]2[CH:15]=[CH:14][N:13]=[C:12]3[N:8]([CH2:7][C:6]4[CH:27]=[CH:28][C:3]([O:2][CH3:1])=[CH:4][CH:5]=4)[N:9]=[C:10]([NH:36][CH:33]4[CH2:34][CH2:35][N:30]([CH3:29])[CH2:31][CH2:32]4)[C:11]=23)=[C:19]([F:25])[CH:20]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 145742L-ProlineHCID 27375314-Amino-1-methylpiperidineHCID 672210033-Fluoro-4-((3-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)oxy)aniline

Product 1

HCID 685163724-(4-amino-2-fluorophenoxy)-1-(4-methoxybenzyl)-N-(1-methylpiperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-amineYield 51.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (0.10 g, 0.20 mmol; prepared as in Example 7, Step B), 1-methylpiperidin-4-amine (0.070 g, 0.61 mmol), (S)-pyrrolidine-2-carboxylic acid (9.4 mg, 0.82 mmol), CuI (7.8 mg, 0.041 mmol), and K2CO3 (0.14 g, 1.0 mmol) was heated in DMSO (4 mL) with sealed tube at 100° C. for 17 hours. The reaction mixture was cooled to ambient temperature and treated with CH2Cl2, washed with water, dried over MgSO4, and concentrated to give crude material which was purified by silica gel flash column chromatography (10% MeOH in CH2Cl2) to afford 49 mg (50%) of the desired product. LRMS (ESI pos) m/e 477.1 (M+1).

Workup

  1. customwith sealed tube at 100° C. for 17 hours
  2. washwashed with water
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customto give crude material which
  6. customwas purified by silica gel flash column chromatography (10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-a018ce4b46614091a7eab0ddd9320a9d
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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