Toluene → Tert-butyl 4-(3-(4-(5-chloropyridin-2-ylamino)phenoxy)pyrazin-2-yl)piperidine-1-carboxylate

HRID 473705Notes

Reaction equation

HRID 473705 reaction equation
[NH2:1][C:2]1[CH:27]=[CH:26][C:5]([O:6][C:7]2[C:8]([CH:13]3[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]3)=[N:9][CH:10]=[CH:11][N:12]=2)=[CH:4][CH:3]=1.Br[C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][N:30]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(C)C=CC=CC=1>C(Cl)Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:35][C:32]1[CH:33]=[CH:34][C:29]([NH:1][C:2]2[CH:27]=[CH:26][C:5]([O:6][C:7]3[C:8]([CH:13]4[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])[CH2:15][CH2:14]4)=[N:9][CH:10]=[CH:11][N:12]=3)=[CH:4][CH:3]=2)=[N:30][CH:31]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 8170982-Bromo-5-chloropyridineHCID 59374021Tert-butyl 4-(3-(4-aminophenoxy)pyrazin-2-yl)piperidine-1-carboxylate

Product 1

HCID 59374009Tert-butyl 4-(3-(4-(5-chloropyridin-2-ylamino)phenoxy)pyrazin-2-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

Into a sealed tube were added tert-butyl 4-(3-(4-aminophenoxy)pyrazin-2-yl)piperidine-1-carboxylate (0.31 g, 0.84 mmol), 2-bromo-5-chloropyridine (0.17 g, 0.92 mmol), palladium (II) acetate (0.019 g, 0.084 mmol), (rac)-BINAP (0.073 g, 0.12 mmol), cesium carbonate (0.49 g, 1.51 mmol), and toluene (4 mL). After the mixture was degassed for 5 min, the reaction was stirred at 100° C. for 18 h. The cooled reaction was diluted with CH2Cl2 and washed with water; the aqueous layer was back-extracted with CH2Cl2 (1×). The organic extracts were combined, dried (MgSO4), filtered, and concentrated in vacuo. Flash column chromatography (10% to 40% EtOAc (10% MeOH)/Hexanes) provided tert-butyl 4-(3-(4-(5-chloropyridin-2-ylamino)phenoxy)-pyrazin-2-yl)piperidine-1-carboxylate as a yellow foam. MS (ESI, pos. ion) m/z: 482.1 (M+1).

Workup

  1. customAfter the mixture was degassed for 5 min
  2. customThe cooled reaction
  3. washwashed with water
  4. extractionthe aqueous layer was back-extracted with CH2Cl2 (1×)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-324c1270580a412c8da438a84393edd6
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

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