Potassium Carbonate → HCID 68513147, compound

HRID 2241337Notes

Reaction equation

HRID 2241337 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]([CH3:36])[C@H:31]1[CH2:35][CH2:34][NH:33][CH2:32]1.C([O-])([O-])=O.[K+].[K+].N1CCC[C@H]1C(O)=O>CS(C)=O.ClCCl>[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]([N:33]4[CH2:34][CH2:35][C@H:31]([N:30]([CH3:36])[CH3:29])[CH2:32]4)[C:11]=23)=[C:19]([F:25])[CH:20]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 145742L-ProlineHCID 7019156(3S)-(-)-3-(Dimethylamino)pyrrolidineHCID 672210033-Fluoro-4-((3-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)oxy)aniline

Product 1

HCID 68513147HCID 68513147, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of 4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (49 mg, 0.1 mmol) (prepared in Example 7, step B) in 300 μL DMSO at ambient temperature in a capped reaction vial was added (S)—N,N-dimethylpyrrolidin-3-amine (19 uL, 0.15 mmol) followed by K2CO3 (27 mg, 0.2 mmol), Cu(I)I (19 mg, 0.01 mmol) and L-proline (2.3 mg, 0.02 mmol). The mixture was heated 90° C. overnight, then the mixture was cooled to room temperature, diluted to 30 mL with dichloromethane and washed with H2O. The organic layer was dried (MgSO4), filtered and concentrated. The crude product was loaded onto a Biotage 12S column with dichloromethane and eluted with 5/95 MeOH/dichloromethane to provide the product as a tan oil (9.5 mg, 20% yield).

Workup

  1. temperaturethe mixture was cooled to room temperature
  2. washwashed with H2O
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. washeluted with 5/95 MeOH/dichloromethane

Sources & evidence

ORD record
ord-905938a1dce147fabd25df1d930b0797
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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