Cesium carbonate → 2-[2-(2,5-Dimethyl-2H-pyrazol-3-ylamino)-5-isopropenyl-pyridin-4-ylamino]-N-methyl-benzamide

HRID 62517Notes

Reaction equation

HRID 62517 reaction equation
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])[C:5]([C:19]([CH3:21])=[CH2:20])=[CH:4][N:3]=1.[CH3:22][N:23]1[C:27]([NH2:28])=[CH:26][C:25]([CH3:29])=[N:24]1.C([O-])([O-])=O.[Cs+].[Cs+].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>CC([O-])=O.CC([O-])=O.[Pd+2].O1CCOCC1>[CH3:22][N:23]1[C:27]([NH:28][C:2]2[CH:7]=[C:6]([NH:8][C:9]3[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=3[C:11]([NH:13][CH3:14])=[O:12])[C:5]([C:19]([CH3:21])=[CH2:20])=[CH:4][N:3]=2)=[CH:26][C:25]([CH3:29])=[N:24]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 5207211,3-Dimethyl-1H-pyrazol-5-amineHCID 634876Binap, (A+-)-HCID 575169072-(2-Chloro-5-isopropenyl-pyridin-4-ylamino)-N-methyl-benzamide

Product 1

HCID 462152722-[2-(2,5-Dimethyl-2H-pyrazol-3-ylamino)-5-isopropenyl-pyridin-4-ylamino]-N-methyl-benzamide

Reagents, catalysts & solvents 2

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

Procedure

To a 10 mL microwave tube was added 2-(2-chloro-5-isopropenyl-pyridin-4-ylamino)-N-methyl-benzamide (0.075 g, 0.25 mmol, 1 eq), 2,5-dimethyl-2H-pyrazol-3-ylamine (0.055 g, 0.50 mmol, 2 eq), Cs2CO3 (0.24 g, 0.74 mmol, 3 eq) and 1,4-dioxane (3 mL). The resulting mixture was degassed with N2 for 30 minutes. Then Pd(OAc)2 (0.015 g, 0.07 mmol, 0.27 eq) and BINAP (0.046 g, 0.074 mmol, 0.3 eq) were added and the mixture degassed again with N2 for another 10 minutes. The resulting reaction mixture was irradiated in a CEM microwave at 110° C. and 150 W for 45 min. The progress of the reaction was monitored by LCMS. After it was complete, Cs2CO3 was removed by filtration and the filtrate was concentrated under reduced pressure. The resulting crude product was purified by column chromatography over neutral alumina using 0.2% MeOH-DCM as the eluant. This gave the title compound as an off white solid (180 mg, 48%). 1H-NMR (400 MHz, DMSO-d6): δ 2.02-2.10 (m, 6H), 2.73-2.74 (d, 3H, J=4.48 Hz), 3.53 (s, 3H), 5.05 (s, 1H), 5.31 (s, 1H), 5.97 (s, 1H), 6.67 (s, 1H), 6.90-7.05 (m, 1H), 7.4-7.55 (m, 2H), 7.61-7.63 (d, 1H, J=7.04 Hz), 7.76 (s, 1H), 8.48 (s, 1H), 8.54-8.67 (brs, 1H), 9.61 (s, 1H). LC-MS [M+H]+=377.4.

Workup

  1. customThe resulting mixture was degassed with N2 for 30 minutes
  2. customthe mixture degassed again with N2 for another 10 minutes
  3. customThe resulting reaction mixture
  4. customwas irradiated in a CEM microwave at 110° C.
  5. customCs2CO3 was removed by filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe resulting crude product was purified by column chromatography over neutral alumina using 0.2% MeOH-DCM as the eluant

Sources & evidence

ORD record
ord-d63649518ca94ee2991a8e06a02cc342
Source dataset
uspto-grants-2016_09
Patent number
US09446034B2

Reaction notes

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