Potassium Carbonate → 2-(4-(1-(4-methoxybenzyl)-3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenylamino)-N-(4-fluorophenyl)nicotinamide

HRID 2241396Notes

Reaction equation

HRID 2241396 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([NH2:8])[CH2:4][CH2:3]1.C([O-])([O-])=O.[K+].[K+].N1CCC[C@H]1C(O)=O.[CH3:23][O:24][C:25]1[CH:66]=[CH:65][C:28]([CH2:29][N:30]2[C:34]3=[N:35][CH:36]=[CH:37][C:38]([O:39][C:40]4[CH:45]=[CH:44][C:43]([NH:46][C:47]5[N:62]=[CH:61][CH:60]=[CH:59][C:48]=5[C:49]([NH:51][C:52]5[CH:57]=[CH:56][C:55]([F:58])=[CH:54][CH:53]=5)=[O:50])=[CH:42][C:41]=4[F:63])=[C:33]3[C:32](I)=[N:31]2)=[CH:27][CH:26]=1>CS(C)=O.O.C(Cl)Cl>[CH3:23][O:24][C:25]1[CH:26]=[CH:27][C:28]([CH2:29][N:30]2[C:34]3=[N:35][CH:36]=[CH:37][C:38]([O:39][C:40]4[CH:45]=[CH:44][C:43]([NH:46][C:47]5[N:62]=[CH:61][CH:60]=[CH:59][C:48]=5[C:49]([NH:51][C:52]5[CH:57]=[CH:56][C:55]([F:58])=[CH:54][CH:53]=5)=[O:50])=[CH:42][C:41]=4[F:63])=[C:33]3[C:32]([NH:8][CH:5]3[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]3)=[N:31]2)=[CH:65][CH:66]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 145742L-ProlineHCID 27375314-Amino-1-methylpiperidineHCID 672218582-(4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenylamino)-N-(4-fluorophenyl)nicotinamide

Product 1

HCID 685161762-(4-(1-(4-methoxybenzyl)-3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenylamino)-N-(4-fluorophenyl)nicotinamideYield 11.7%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A 25 mL round-bottomed flask was charged with Cu(I)I (0.0108 g, 0.0568 mmol), 1-methylpiperidin-4-amine (0.0973 g, 0.852 mmol), K2CO3 (0.196 g, 1.42 mmol), L-Proline (0.0131 g, 0.114 mmol) and DMSO (2.5 mL). The reaction mixture was stirred for 5 minutes and 2-(4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenylamino)-N-(4-fluorophenyl)nicotinamide (0.200 g, 0.284 mmol) in DMSO (2.5 mL) was added. The reaction mixture was heated to 100° C. for 18 hours. The reaction mixture was cooled to ambient temperature and DCM and water (10 mL) were added. The organic layer washed with brine, dried over sodium sulfate, filtered and concentrated. The crude material was purified by silica gel chromatography, eluting with EtOAc to provide the product (23 mg, 11%). LRMS M−1 (691.2) observed.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. washThe organic layer washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by silica gel chromatography
  7. washeluting with EtOAc

Sources & evidence

ORD record
ord-00f80b82dfec43baad7501069cb573f0
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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