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

HRID 2241407Notes

Reaction equation

HRID 2241407 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][O:30][CH2:31][CH2:32][N:33]1[CH2:38][CH2:37][CH:36]([NH2:39])[CH2:35][CH2:34]1.N1CCC[C@H]1C(O)=O.C([O-])([O-])=O.[K+].[K+]>[Cu]I.CS(C)=O>[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]([NH:39][CH:36]3[CH2:37][CH2:38][N:33]([CH2:32][CH2:31][O:30][CH3:29])[CH2:34][CH2:35]3)=[N:9]2)=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 145742L-ProlineHCID 201191211-(2-Methoxyethyl)piperidin-4-amineHCID 672210033-Fluoro-4-((3-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)oxy)aniline

Product 1

HCID 685134661-(4-methoxybenzyl)-4-(4-amino-2-fluorophenoxy)-N-(1-(2-methoxyethyl)piperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (0.123 g, 0.25 mmol, prepared according to Example 7, Step B), 1-(2-methoxyethyl)piperidin-4-amine (0.119 g, 0.750 mmol), copper(I)iodide (0.00952 g, 0.0500 mmol), (S)-pyrrolidine-2-carboxylic acid (0.0115 g, 0.100 mmol), K2CO3 (0.173 g, 1.25 mmol), and DMSO (0.5 mL) was stirred at 100° C. for 3 days in a sealed vessel. The reaction was partitioned between EtOAc and water. The phases were separated and the aqueous phase was re-extracted with EtOAc. The combined organic phases were washed with water, dried (Na2SO4), filtered, and concentrated. The crude was purified by preparative TLC (1 mm thickness) eluting with 10% MeOH/CHCl3. Yield: 42 mg (32%). LRMS (APCI+): 100% purity, 220 nm, m/z 521 (M+1) detected.

Workup

  1. customThe reaction was partitioned between EtOAc and water
  2. customThe phases were separated
  3. extractionthe aqueous phase was re-extracted with EtOAc
  4. washThe combined organic phases were washed with water
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude was purified by preparative TLC (1 mm thickness)
  9. washeluting with 10% MeOH/CHCl3

Sources & evidence

ORD record
ord-92f72b24e97a46c1bc6aeb217a344105
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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