Cesium carbonate → HCID 46214778, compound

HRID 62489Notes

Reaction equation

HRID 62489 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]([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][O: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 575168962-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide

Product 1

HCID 46214778HCID 46214778, compoundYield 24%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
160 °C

Procedure

A 20-mL microwave tube was charged with 2-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide (100 mg, 0.320 mmol), 1-ethyl-3-methyl-1H-pyrazol-5-amine (60.1 mg, 0.481 mmol), cesium carbonate (313 mg, 0.961 mmol), 1,4-dioxane (5.0 mL) and THF (1.0 mL). The reaction mixture was degassed by nitrogen for 10 min. (±)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthalene (19.95 mg, 0.032 mmol) and Palladium(II) acetate (3.60 mg, 0.016 mmol) in minimum amount of 1,4-dioxane were then added. The tube was sealed and 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 (16 mg, 24% yield) MS: M(C19H21ClN6O2)=400.86, (M+H)+=401; 1H NMR (400 MHz, MeOD) δ ppm 7.92 (s, 1 H) 7.44-7.66 (m, 3 H) 7.11-7.25 (m, 1 H) 6.61 (s, 1 H) 5.99 (s, 1 H) 3.98 (q, J=7.3 Hz, 2 H) 3.80 (s, 3 H) 2.21 (s, 3 H) 1.32 (t, J=7.2 Hz, 3 H).

Workup

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

Sources & evidence

ORD record
ord-5a1115aac7ca4e15b82f18531c5c5fcb
Source dataset
uspto-grants-2016_09
Patent number
US09446034B2

Reaction notes

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