Aniline → HCID 57484939, compound

HRID 475981Notes

Reaction equation

HRID 475981 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:26])[NH:20][C:21]([CH3:25])=[CH:22][C:23]=2[CH3:24])=[O:15])[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH3:24][C:23]1[CH:22]=[C:21]([CH3:25])[NH:20][C:19](=[O:26])[C:18]=1[CH2:17][NH:16][C:14]([C:4]1[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=[C:2]([NH:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:3]=1)=[O:15]

Participants

7

Reactant 4

HCID 6115AnilineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 565974256-Chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

Product 1

HCID 57484939HCID 57484939, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

To a 10 mL microwave vial were sequentially added 6-chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (0.100 g, 0.267 mmol), cesium carbonate (0.305 g, 0.936 mmol), 1,4-Dioxane (2.5 mL) and aniline (0.049 mL, 0.535 mmol). The stirring suspension was degassed with nitrogen for 10 min. Added next were BINAP (0.033 g, 0.053 mmol) and palladium(II) acetate (6.01 mg, 0.027 mmol). The sealed mixture was stirred at 105° C. overnight. After cooling to room temperature, the contents were poured onto EtOAc and filtered through Celite. The filter pad was washed with additional 50% THF/EtOAc. The combined filtrates were treated with silica gel and concentrated in vacuo. The crude product was purified by silica gel chromatography (dry loaded, eluent: Gradient 5-80% of DCM and chloroform containing 10% 2M Ammonia (in methanol))). The isolated solid was dried in a vacuum oven overnight and the final product collected as 0.061 g (52%). LCMS E-S (M+H)=431.3. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.50 (d, J=6.57 Hz, 6H), 2.13 (s, 3H), 2.23 (s, 3H), 4.35 (d, J=5.05 Hz, 2H), 4.98-5.11 (m, 1H), 5.90 (s, 1H), 6.93-7.00 (m, 2H), 7.34 (t, J=7.96 Hz, 2H), 7.86 (d, J=7.58 Hz, 2H), 7.97 (s, 1H), 8.59 (t, J=5.05 Hz, 1H), 9.62 (s, 1H), 11.58 (br. s., 1H).

Workup

  1. customThe stirring suspension was degassed with nitrogen for 10 min
  2. additionAdded next
  3. temperatureAfter cooling to room temperature
  4. additionthe contents were poured onto EtOAc
  5. filtrationfiltered through Celite
  6. washThe filter pad was washed with additional 50% THF/EtOAc
  7. additionThe combined filtrates were treated with silica gel
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by silica gel chromatography (dry loaded, eluent: Gradient 5-80% of DCM and chloroform containing 10% 2M Ammonia (in methanol)))
  10. customThe isolated solid was dried in a vacuum oven overnight
  11. customthe final product collected as 0.061 g (52%)

Sources & evidence

ORD record
ord-6372b738069d47a9b9267d36da381763
Source dataset
uspto-grants-2014_01
Patent number
US08637509B2

Reaction notes

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