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

HRID 1472561Notes

Reaction equation

HRID 1472561 reaction equation
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:19]=[CH:18][CH:17]=[CH:16][C:10]=2[C:11]([NH:13][O:14][CH3:15])=[O:12])[C:5]([CH:20]2[CH2:22][CH2:21]2)=[CH:4][N:3]=1.[CH2:23]([N:25]1[C:29]([NH2:30])=[CH:28][C:27]([CH3:31])=[N:26]1)[CH3:24].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:20]1([C:5]2[C:6]([NH:8][C:9]3[CH:19]=[CH:18][CH:17]=[CH:16][C:10]=3[C:11]([NH:13][O:14][CH3:15])=[O:12])=[CH:7][C:2]([NH:30][C:29]3[N:25]([CH2:23][CH3:24])[N:26]=[C:27]([CH3:31])[CH:28]=3)=[N:3][CH:4]=2)[CH2:22][CH2:21]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27683831-Ethyl-3-methyl-1H-pyrazol-5-amineHCID 575169062-(2-Chloro-5-cyclopropyl-pyridin-4-ylamino)-N-methoxy-benzamide

Product 1

HCID 462152712-[5-Cyclopropyl-2-(2-ethyl-5-methyl-2H-pyrazol-3-ylamino)-pyridin-4-ylamino]-N-methoxy-benzamide

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-methoxy-benzamide (0.075 g, 0.24 mmol, 1 eq), 2-ethyl-5-methyl-2H-pyrazol-3-ylamine (0.05 g, 0.36 mmol, 1.5 eq), Cs2CO3 (0.23 g, 0.71 mmol, 3 eq), and 1,4-dioxane (3 mL) and the resulting mixture was degassed with N2 for 15 min. To this was added Pd2(dba)3 (0.014 g, 0.014 mmol, 0.06 eq) and xanthphos (0.03 g, 0.06 mmol, 0.25 eq) and this mixture was again degassed with N2 for another 10 min. The resulting mixture was irradiated in a CEM microwave at 120° C., 150 W for 35 min. After the reaction was finished solvent was removed under reduced pressure and crude product was purified by column chromatography over silica gel (100-200 mesh) using 1% MeOH-DCM as the eluant followed by washing with diethyl ether and pentane and DCM to give the title compound as an off white solid (5 mg, 5%). 1H-NMR (400 MHz, DMSO-d6): δ 0.50-0.60(m, 2H), 0.88-1.00 (m, 2H), 1.15-1.27 (m, 3H), 1.55-1.65 (m, 1H), 2.07 (s, 3H), 3.70 (s, 3H), 3.80-3.95 (m, 2H), 5.95 (s, 1H), 6.64 (s, 1H), 6.90-7.10 (m, 1H), 7.40-7.60 (m, 3H), 7.72 (s, 1H), 8.34 (s, 1H), 9.47 (s, 1H), 11.88 (brs, 1H). LC-MS [M+H]+=407.3.

Workup

  1. customthe resulting mixture was degassed with N2 for 15 min
  2. customthis mixture was again degassed with N2 for another 10 min
  3. customThe resulting mixture was irradiated in a CEM microwave at 120° C.
  4. customwas removed under reduced pressure and crude product
  5. customwas purified by column chromatography over silica gel (100-200 mesh)
  6. washby washing with diethyl ether and pentane and DCM

Sources & evidence

ORD record
ord-2c0969f5c45d4373ac4b2777661b1ba9
Source dataset
uspto-grants-2015_04
Patent number
US09012479B2

Reaction notes

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