1-Butanol → N-Methyl-3-(2-(2-oxoindolin-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)picolinamide

HRID 1887696Notes

Reaction equation

HRID 1887696 reaction equation
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[C:10]([C:15]([NH:17][CH3:18])=[O:16])=[N:11][CH:12]=[CH:13][CH:14]=2)[C:5]([C:19]([F:22])([F:21])[F:20])=[CH:4][N:3]=1.[NH2:23][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[NH:29][C:28](=[O:33])[CH2:27]2.CCCCO.Cl>CCOC(C)=O>[CH3:18][NH:17][C:15](=[O:16])[C:10]1[C:9]([NH:8][C:6]2[C:5]([C:19]([F:22])([F:21])[F:20])=[CH:4][N:3]=[C:2]([NH:23][C:24]3[CH:25]=[C:26]4[C:30](=[CH:31][CH:32]=3)[NH:29][C:28](=[O:33])[CH2:27]4)[CH:7]=2)=[CH:14][CH:13]=[CH:12][N:11]=1

Participants

6

Reactant 4

HCID 2631-ButanolHCID 313Hydrochloric AcidHCID 27732135-Amino-2-oxindoleHCID 581551313-(2-Chloro-5-(trifluoromethyl)pyridin-4-ylamino)-N-methylpicolinamide

Product 1

HCID 66958173N-Methyl-3-(2-(2-oxoindolin-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)picolinamideYield 56%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
160 °C

Procedure

To a high pressure vial was added 3-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-N-methylpicolinamide (0.205 g, 0.62 mmol) and 5-aminoindolin-2-one (0.138 g, 1.2 eq) and n-BuOH (5 mL). HCl (˜1.25M HCl in ethanol, 0.5 mL, 1.0 eq) was added to the above mixture. The vial was sealed and heated at 160° C. with stirring overnight in an oil bath. The mixture was cooled to room temperature and concentrated under reduced pressure to obtain the crude. The crude was dissolved in EtOAc and washed with saturated NaHCO3 solution. The organic layers were concentrated and the crude was purified by silica gel chromatography (20%˜100% EtOAc/Hex). The product was precipitated from EtOAc and filtered to obtain the desired product as the free base (isolated yield 56%). The product was converted to the HCl salt.

Workup

  1. customThe vial was sealed
  2. temperatureThe mixture was cooled to room temperature
  3. concentrationconcentrated under reduced pressure
  4. customto obtain the crude
  5. washwashed with saturated NaHCO3 solution
  6. concentrationThe organic layers were concentrated
  7. customthe crude was purified by silica gel chromatography (20%˜100% EtOAc/Hex)
  8. customThe product was precipitated from EtOAc
  9. filtrationfiltered

Sources & evidence

ORD record
ord-b647b9a731c4447eb6d4a9a7e09ad627
Source dataset
uspto-grants-2013_08
Patent number
US08501763B2

Reaction notes

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