Cesium carbonate → 2-[[5-Chloro-2-[(1-ethyl-3-methyl-1H-pyrazol-5-yl)amino]-4-pyridinyl]amino]-N-ethylbenzamide

HRID 1472542Notes

Reaction equation

HRID 1472542 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][CH2:14][CH3:15])=[O:12])[C:5]([Cl:20])=[CH:4][N:3]=1.[CH2:21]([N:23]1[C:27]([NH2:28])=[CH:26][C:25]([CH3:29])=[N:24]1)[CH3:22].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1.C1COCC1>[Cl:20][C:5]1[C:6]([NH:8][C:9]2[CH:19]=[CH:18][CH:17]=[CH:16][C:10]=2[C:11]([NH:13][CH2:14][CH3:15])=[O:12])=[CH:7][C:2]([NH:28][C:27]2[N:23]([CH2:21][CH3:22])[N:24]=[C:25]([CH3:29])[CH:26]=2)=[N:3][CH:4]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 27683831-Ethyl-3-methyl-1H-pyrazol-5-amineHCID 57516899HCID 57516899, compound

Product 1

HCID 462149312-[[5-Chloro-2-[(1-ethyl-3-methyl-1H-pyrazol-5-yl)amino]-4-pyridinyl]amino]-N-ethylbenzamideYield 35%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
160 °C

Procedure

A vessel was charged with 2-[(2,5-dichloro-4-pyridinyl)amino]-N-ethylbenzamide (100 mg, 0.322 mmol), 1-ethyl-3-methyl-1H-pyrazol-5-amine (60.5 mg, 0.484 mmol), cesium carbonate (315 mg, 0.967 mmol), 1,4-dioxane (5.0 mL), and THF (1.0 mL). The reaction mixture was degassed by nitrogen for 10 min at which time (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (40.1 mg, 0.064 mmol) and palladium (II) acetate (7.24 mg, 0.032 mmol) in a minimum amount of 1,4-dioxane were added. The vessel was sealed and the reaction mixture was heated in microwave oven 160° C. for 40 min. The resulting suspension was cooled to room temperature and filtered through celite. The filtrate was evaporated to dryness and the crude reaction mixture was purified by reverse-phase HPLC to give the title compound as a solid (45 mg, 30% yield); MS: M(C20H23ClN6O)=398.89, (M+H)+=399, 401; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.34 (s, 1 H) 7.94 (s, 1 H) 7.66 (br. s., 1 H) 7.51 (d, J=7.8 Hz, 1 H) 7.31-7.47 (m, 2 H) 6.96-7.17 (m, 1 H) 6.58 (s, 1 H) 6.19 (t, J=5.2 Hz, 1 H) 5.86 (s, 1H) 4.01 (q, J=7.3 Hz, 2 H) 3.42-3.62 (m, 2 H) 2.24 (s, 3 H) 1.37 (t, J=7.3 Hz, 3 H) 1.26 (t, J=7.3 Hz, 3 H).

Workup

  1. additionwere added
  2. customThe vessel was sealed
  3. temperatureThe resulting suspension was cooled to room temperature
  4. filtrationfiltered through celite
  5. customThe filtrate was evaporated to dryness
  6. customthe crude reaction mixture
  7. customwas purified by reverse-phase HPLC

Sources & evidence

ORD record
ord-71c93b5c3e2f46a0af18042ec6c62cc9
Source dataset
uspto-grants-2015_04
Patent number
US09012479B2

Reaction notes

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