Cesium carbonate → [5-(4-Methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-amine

HRID 472341Notes

Reaction equation

HRID 472341 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.Br[C:44]1[CH:57]=[CH:56][C:47]([O:48][CH2:49][CH2:50][N:51]2[CH2:55][CH2:54][CH2:53][CH2:52]2)=[CH:46][CH:45]=1.[CH3:58][S:59]([C:62]1[CH:67]=[CH:66][C:65]([C:68]2[N:73]3[N:74]=[C:75]([NH2:77])[N:76]=[C:72]3[CH:71]=[CH:70][CH:69]=2)=[CH:64][CH:63]=1)(=[O:61])=[O:60].C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH3:58][S:59]([C:62]1[CH:67]=[CH:66][C:65]([C:68]2[N:73]3[N:74]=[C:75]([NH:77][C:44]4[CH:57]=[CH:56][C:47]([O:48][CH2:49][CH2:50][N:51]5[CH2:55][CH2:54][CH2:53][CH2:52]5)=[CH:46][CH:45]=4)[N:76]=[C:72]3[CH:71]=[CH:70][CH:69]=2)=[CH:64][CH:63]=1)(=[O:60])=[O:61]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 70657N-(2-(p-bromophenoxy)ethyl)pyrrolidineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 674790495-(4-(Methylsulfonyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine

Product 1

HCID 59590148[5-(4-Methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[4-(2-pyrrolidin-1-yl-ethoxy)-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 (16.0 mg, 0.0000713 mol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (41.0 mg, 0.0713 mmol), 1,4-dioxane (5 mL), 1-[2-(4-bromo-phenoxy)-ethyl]-pyrrolidine (87 μL, 0.412 mmol), 5-(4-methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (100.0 mg, 0.346 mmol), and cesium carbonate (240 mg, 0.73 mmol) were added all-at-once. The reaction mixture was evacuated with high vacuum and repressurized with nitrogen three times. The tube was sealed and heated at 80° C. for 24 hours. The mixture was cooled to room temperature, filtered through a plug of diatomaceous earth, rinsed with dichloromethane and evaporated. The material was purified via chromatography utilizing an ISCO automated purification apparatus using a silica gel column (40 g) with 0%→20% methanol in dichloromethane solvent gradient. [5-(4-Methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-amine was isolated as an orange gummy solid (0.011 g, 7%). 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.47 (s, 1H), 8.32 (d, J=8.5 Hz, 2H), 8.13 (d, J=8.5 Hz, 2H), 7.67 (m, 2H), 7.59 (d, J=9.6 Hz, 2H), 7.28 (d, J=6.4 Hz, 1H). 6.91 (d, J=8.5 Hz, 2H), 4.10 (br s, 2H), 3.34 (s, 3H), 2.54 (s, 2H), 1.78 (br s, 2H), 1.24 (br s, 2H). MS=478 (MH)+.

Workup

  1. customTo an oven dried tube
  2. additionwere added all-at-once
  3. customThe reaction mixture was evacuated with high vacuum
  4. customThe tube was sealed
  5. temperatureThe mixture was cooled to room temperature
  6. filtrationfiltered through a plug of diatomaceous earth
  7. washrinsed with dichloromethane
  8. customevaporated
  9. customThe material was purified via chromatography
  10. custompurification apparatus

Sources & evidence

ORD record
ord-b2a3e1a5eccd4b82946edcffd1257000
Source dataset
uspto-grants-2014_01
Patent number
US08633173B2

Reaction notes

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