tert-butyl 4-(3-(4-(pyridin-2-ylamino)phenoxy)pyrazin-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate → Tert-butyl 4-(3-(4-(pyridin-2-ylamino)phenoxy)pyrazin-2-yl)piperidine-1-carboxylate

HRID 473708Notes

Reaction equation

HRID 473708 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]1[CH:33]=[CH:32][C:11]([O:12][C:13]2[C:14]([C:19]3[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH:20]=3)=[N:15][CH:16]=[CH:17][N:18]=2)=[CH:10][CH:9]=1>[OH-].[OH-].[Pd+2].C1COCC1>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]1[CH:9]=[CH:10][C:11]([O:12][C:13]2[C:14]([CH:19]3[CH2:20][CH2:21][N:22]([C:25]([O:27][C:28]([CH3:29])([CH3:30])[CH3:31])=[O:26])[CH2:23][CH2:24]3)=[N:15][CH:16]=[CH:17][N:18]=2)=[CH:32][CH:33]=1

Participants

4

Reactant 1

HCID 59374036tert-butyl 4-(3-(4-(pyridin-2-ylamino)phenoxy)pyrazin-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 59374121Tert-butyl 4-(3-(4-(pyridin-2-ylamino)phenoxy)pyrazin-2-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a N2 purged flask containing tert-butyl 4-(3-(4-(pyridin-2-ylamino)phenoxy)pyrazin-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (10.0 g, 22.45 mmol) and pearlman's catalyst (4.1 g, 5.84 mmol) was added THF (350 mL). H2 was bubbled through the solution for 4 minutes, then the solution was capped with a balloon of H2. After 48 hours, LC-MS shows complete conversion. The solution was filtered over a pad of celite, and the celite washed with EtOAc (150 mL). The filtrate was concentrated in vacuo. The residue was taken up in DCM (50 mL) and loaded onto a plug of silica gel (800 mL frit) and eluted with 0% to 50% EtOAc in hexanes to give tert-butyl 4-(3-(4-(pyridin-2-ylamino)phenoxy)pyrazin-2-yl)piperidine-1-carboxylate as a light yellow foam. MS (ESI, pos. ion) m/z: 448.1 (M+1).

Workup

  1. customH2 was bubbled through the solution for 4 minutes
  2. customthe solution was capped with a balloon of H2
  3. filtrationThe solution was filtered over a pad of celite
  4. washthe celite washed with EtOAc (150 mL)
  5. concentrationThe filtrate was concentrated in vacuo
  6. washeluted with 0% to 50% EtOAc in hexanes

Sources & evidence

ORD record
ord-f5614caebba34f2488b0b2a889dec4ae
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

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