Cesium carbonate → [8-(2-Methoxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-(4-morpholin-4-yl-phenyl)-amine

HRID 472256Notes

Reaction equation

HRID 472256 reaction equation
CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.[CH3:43][O:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=1[C:51]1[C:52]2[N:53]([N:57]=[C:58]([NH2:60])[N:59]=2)[CH:54]=[CH:55][CH:56]=1.Br[C:62]1[CH:67]=[CH:66][C:65]([N:68]2[CH2:73][CH2:72][O:71][CH2:70][CH2:69]2)=[CH:64][CH:63]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH3:43][O:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=1[C:51]1[C:52]2[N:53]([N:57]=[C:58]([NH:60][C:62]3[CH:63]=[CH:64][C:65]([N:68]4[CH2:69][CH2:70][O:71][CH2:72][CH2:73]4)=[CH:66][CH:67]=3)[N:59]=2)[CH:54]=[CH:55][CH:56]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 116228514-(4-Bromophenyl)morpholineHCID 575023708-(2-Methoxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine

Product 1

HCID 49838139[8-(2-Methoxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-(4-morpholin-4-yl-phenyl)-amine

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To an oven dried tube was added palladium acetate (10.0 mg, 0.0445 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (75.0 mg, 0.130 mmol), 8-(2-methoxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (100.0 mg, 0.4162 mmol), 4-(4-bromo-phenyl)-morpholine (120.0 mg, 0.4956 mmol), cesium carbonate (270 mg, 0.83 mmol) and 1,4-dioxane (5 mL). The tube was evacuated and backflushed with nitrogen three times. The tube was sealed and heated at 80° C. for 72 hours. The mixture was cooled to room temperature, diluted with dichloromethane (10 mL), filtered through a plug of diatomaceous earth, rinsed with dichloromethane and evaporated. The material was purified via chromatography utilizing an ISCO automated purification apparatus (amine modified silica gel column 5%→100% ethyl acetate in hexanes). The title compound, [8-(2-Methoxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-(4-morpholin-4-yl-phenyl)-amine, was isolated as a pale yellow foam (0.034 g, 20%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.39 (dd, J=6.7, 1.1 Hz, 1H), 7.61 (dd, J=7.5, 1.7 Hz, 1H), 7.51 (dd, J=7.3, 0.9 Hz, 1H), 7.50-7.45 (m, 2H), 7.43-7.37 (m, 1H), 7.12-7.07 (m, 1H), 7.05 (d, J=8.2, 1H), 6.96-6.87 (m, 3H), 6.67 (s, 1H), 3.89-3.85 (m, 4H), 3.81 (s, 3H), 3.12-3.08 (m, 4H). MS=402 (MH)+.

Workup

  1. customTo an oven dried tube
  2. customThe tube was evacuated
  3. customThe tube was sealed
  4. temperatureThe mixture was cooled to room temperature
  5. additiondiluted with dichloromethane (10 mL)
  6. filtrationfiltered through a plug of diatomaceous earth
  7. washrinsed with dichloromethane
  8. customevaporated
  9. customThe material was purified via chromatography
  10. custompurification apparatus (amine modified silica gel column 5%→100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-cb2e4f56761f40078cc8f1a7fa7fcf86
Source dataset
uspto-grants-2014_01
Patent number
US08633173B2

Reaction notes

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