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

HRID 1472560Notes

Reaction equation

HRID 1472560 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.[CH3:23][N:24]1[C:28]([NH2:29])=[CH:27][C:26]([CH3:30])=[N:25]1.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:29][C:28]3[N:24]([CH3:23])[N:25]=[C:26]([CH3:30])[CH:27]=3)=[N:3][CH:4]=2)[CH2:22][CH2:21]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 5207211,3-Dimethyl-1H-pyrazol-5-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 575169062-(2-Chloro-5-cyclopropyl-pyridin-4-ylamino)-N-methoxy-benzamide

Product 1

HCID 462152702-[5-Cyclopropyl-2-(2,5-dimethyl-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), 2,5-dimethyl-2H-pyrazol-3-ylamine (0.05 g, 0.47 mmol, 2 eq), Cs2CO3 (0.23 g, 0.71 mmol, 3 eq), and 1,4-dioxane (3 mL). The resulting mixture was degassed with N2 for 15 min. To this was added Pd2(dba)3 (0.015 g, 0.014 mmol, 0.06 eq) and xanthphos (0.03 g, 0.06 mmol, 0.25 eq) and the mixture was again degassed with N2 for 30 min. The resulting mixture was irradiated in a CEM microwave at 120° C., 150 W for 35 min. After completion of reaction, solvent was removed under reduced pressure and crude compound was purified using column chromatography over silica gel (100-200 mesh) using 1% MeOH-DCM as the eluant followed by prep HPLC. Solid compound so obtained was washed with diethyl ether and pentane to give the title compound as an off white solid (11 mg, 12%). 1H-NMR (400 MHz, DMSO-d6): δ 0.52-0.60 (m, 2H), 0.82-1.00 (m, 2H), 1.50-1.62 (m, 1H), 2.05 (s, 3H), 3.52 (s, 3H), 3.70 (s, 3H), 5.96 (s, 1H), 6.67 (s, 1H), 6.98-7.10 (m, 1H), 7.40-7.60 (m, 3H), 7.73 (s, 1H), 8.39 (s, 1H), 9.46 (s, 1H), 11.88 (brs, 1H). LC-MS [M+H]+=393.4.

Workup

  1. customThe resulting mixture was degassed with N2 for 15 min
  2. customthe mixture was again degassed with N2 for 30 min
  3. customThe resulting mixture was irradiated in a CEM microwave at 120° C.
  4. customAfter completion of reaction, solvent
  5. customwas removed under reduced pressure and crude compound
  6. customwas purified
  7. customSolid compound so obtained
  8. washwas washed with diethyl ether and pentane

Sources & evidence

ORD record
ord-140a1399ffaa4be3bf1af91b537d99b6
Source dataset
uspto-grants-2015_04
Patent number
US09012479B2

Reaction notes

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