Cesium carbonate → N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(4-(morpholinomethyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine

HRID 336408Notes

Reaction equation

HRID 336408 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:30]=[C:12]3[CH:13]=[CH:14][CH:15]=[C:16]([C:17]4[CH:22]=[CH:21][C:20]([CH2:23][N:24]5[CH2:29][CH2:28][O:27][CH2:26][CH2:25]5)=[CH:19][CH:18]=4)[N:11]3[N:10]=2)=[CH:4][CH:3]=1.[CH3:31][N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>O1CCOCC1.CCOC(C)=O.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]>[CH3:31][N:32]1[CH2:37][CH2:36][N:35]([C:2]2[CH:7]=[CH:6][C:5]([NH:8][C:9]3[N:30]=[C:12]4[CH:13]=[CH:14][CH:15]=[C:16]([C:17]5[CH:22]=[CH:21][C:20]([CH2:23][N:24]6[CH2:29][CH2:28][O:27][CH2:26][CH2:25]6)=[CH:19][CH:18]=5)[N:11]4[N:10]=3)=[CH:4][CH:3]=2)[CH2:34][CH2:33]1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 531671-MethylpiperazineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 59186222N-(4-chlorophenyl)-5-(4-(morpholinomethyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine

Product 1

HCID 59186465N-(4-(4-methylpiperazin-1-yl)phenyl)-5-(4-(morpholinomethyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amineYield 11%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
160 °C

Procedure

A suspension of N-(4-chlorophenyl)-5-(4-(morpholinomethyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine (300 mg, 0.7 mmol), 1-methylpiperazine (356 mg, 3.6 mmol), tris(dibenzylideneacetone)dipalladium (0) (65 mg, 0.07 mmol), cesium carbonate (456 mg, 1.4 mmol), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (410 mg, 0.07 mmol) in 1,4-dioxane (2 mL) was irradiated by microwave heating to 160° C. for 20 min. The reaction mixture was diluted with EtOAc (300 mL), and filtered though celite. The filtrate was concentrated to give a black residue, which was purified by preparative thin layer chromatography (10% methanol in dichloromethane) to afford product (38.9 mg 11% yield). 1H NMR (400 MHz, CDCl3), δ: 7.96 (d, J=8 Hz, 2H), 7.52-7.42 (m, 6H), 6.92-6.87 (m, 3H), 6.68 (m, 1H), 3.79-3.72 (m, 4H), 3.59 (s, 2H), 3.18-3.12 (m, 4H), 2.6-2.55 (m 4H), 2.55-2.48 (m, 4H), 2.33 (s, 3H). LCMS (ESI) m/z: 484.1.

Workup

  1. customwas irradiated by microwave
  2. filtrationfiltered though celite
  3. concentrationThe filtrate was concentrated
  4. customto give a black residue, which
  5. customwas purified by preparative thin layer chromatography (10% methanol in dichloromethane)
  6. customto afford product (38.9 mg 11% yield)

Sources & evidence

ORD record
ord-9f2396ad4a0644989f3522aca6503930
Source dataset
uspto-grants-2014_11
Patent number
US08889673B2

Reaction notes

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