Cesium carbonate → 6-Chloro-N-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)-[1,2,4]-triazolo[1,5-a]pyridin-8-amine

HRID 1024036Notes

Reaction equation

HRID 1024036 reaction equation
Br[C:2]1[C:3]2[N:4]([N:9]=[CH:10][N:11]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[O:12]1[CH2:15][CH:14]([N:16]2[CH2:21][CH2:20][N:19]([C:22]3[CH:23]=[CH:24][C:25]([NH2:28])=[N:26][CH:27]=3)[CH2:18][CH2:17]2)[CH2:13]1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>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].O1CCOCC1>[Cl:8][C:6]1[CH:7]=[C:2]([NH:28][C:25]2[CH:24]=[CH:23][C:22]([N:19]3[CH2:20][CH2:21][N:16]([CH:14]4[CH2:13][O:12][CH2:15]4)[CH2:17][CH2:18]3)=[CH:27][N:26]=2)[C:3]2[N:4]([N:9]=[CH:10][N:11]=2)[CH:5]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866841255-[4-(3-Oxetanyl)-1-piperazinyl]-2-pyridinamineHCID 866841358-Bromo-6-chloro-(1,2,4)triazolo(1,5-a)pyridine

Product 1

HCID 866841346-Chloro-N-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)-[1,2,4]-triazolo[1,5-a]pyridin-8-amineYield 64.8%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
105 °C

Procedure

A 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with 1,4-dioxane (8 mL), 108c (250 mg, 1.07 mmol), 5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-amine (252 mg, 1 mmol), and cesium carbonate (700 mg, 2 mmol). Xantphos (30 mg, 0.08 mmol) and Pd2(dba)3 (55 mg, 0.08 mmol) were added, and the reaction mixture was heated at 105° C. for 3 h. After this time the reaction was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel chromatography eluting with CH2Cl2/MeOH (20:1) to afford 108d (250 mg, 60%). MS: [M+H]+ 386.

Workup

  1. customA 25-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. temperaturereflux condenser
  3. temperatureAfter this time the reaction was cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by silica gel chromatography
  7. washeluting with CH2Cl2/MeOH (20:1)

Sources & evidence

ORD record
ord-e3337a395ce544a1b057cdf948eaa7bd
Source dataset
uspto-grants-2014_05
Patent number
US08722676B2

Reaction notes

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