Cesium carbonate → 2-[5-Cyclopropyl-2-(2-ethyl-5-methyl-2H-pyrazol-3-ylamino)-pyridin-4-ylamino]-N-methylbenzamide

HRID 1472557Notes

Reaction equation

HRID 1472557 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]([CH:19]2[CH2:21][CH2:20]2)=[CH:4][N:3]=1.[CH2:22]([N:24]1[C:28]([NH2:29])=[CH:27][C:26]([CH3:30])=[N:25]1)[CH3:23].C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[CH:19]1([C:5]2[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])=[CH:7][C:2]([NH:29][C:28]3[N:24]([CH2:22][CH3:23])[N:25]=[C:26]([CH3:30])[CH:27]=3)=[N:3][CH:4]=2)[CH2:21][CH2:20]1

Participants

7

Reactant 4

HCID 10796Cesium carbonate2×HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27683831-Ethyl-3-methyl-1H-pyrazol-5-amineHCID 575169032-(2-Chloro-5-cyclopropyl-pyridin-4-ylamino)-N-methyl-benzamide

Product 1

HCID 462152692-[5-Cyclopropyl-2-(2-ethyl-5-methyl-2H-pyrazol-3-ylamino)-pyridin-4-ylamino]-N-methylbenzamideYield 20.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a 10 mL microwave tube were added 2-(2-chloro-5-cyclopropyl-pyridin-4-ylamino)-N-methyl-benzamide (0.075 g, 0.25 mmol, 1 eq), 2-ethyl-5-methyl-2H-pyrazol-3-ylamine (0.035 g, 0.27 mmol, 1.1 eq), Cs2CO3 (0.23 g, 0.70 mmol, 2.8 eq) and 1,4-dioxane (3 mL) and the resulting mixture was degassed with N2 for 30 minutes. To this mixture was added Pd2(dba)3 (0.008 g, 0.007 mmol, 0.03 eq) and xanthphos (0.009 g, 0.015 mmol, 0.06 eq) and this mixture was 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 completion of the reaction, Cs2CO3 was removed by filtration and the filtrate was concentrated under reduced pressure to give a crude product. It was purified using column chromatography over neutral alumina using 0.2% MeOH-DCM as the eluant. The solid compound so obtained was washed with diethyl ether and hexane to give the title compound as a white solid (20 mg, 20%). 1H-NMR (400 MHz, DMSO-d6): δ 0.50-0.62 (m, 2H), 0.88-0.99 (m, 2H), 1.15-1.28 (m, 3 H), 1.55-1.65 (m, 1H), 2.07 (s, 3H), 2.76-2.77 (d, 3H, J=4.36 Hz), 3.82-3.95 (m, 2H), 5.95 (s, 1H), 6.68 (s, 1H), 6.99-7.10 (m, 1H), 7.42-7.50 (m, 1H), 7.50-7.55 (m, 1H) 7.64-7.66 (d, 1H, J=7.6 Hz), 7.71 (s, 1H), 8.30 (s, 1H), 8.55-8.70 (brs, 1H), 9.95 (s, 1H). LC-MS [M+H]+=391.4.

Workup

  1. customthe resulting mixture was degassed with N2 for 30 minutes
  2. customthis mixture was degassed again with N2 for another 10 minutes
  3. customThe resulting reaction mixture
  4. customwas irradiated in a CEM microwave at 110° C.
  5. customwas removed by filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customto give a crude product
  8. customIt was purified
  9. customThe solid compound so obtained
  10. washwas washed with diethyl ether and hexane

Sources & evidence

ORD record
ord-cd525f0a03104b7e97db287a34da3a60
Source dataset
uspto-grants-2015_04
Patent number
US09012479B2

Reaction notes

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