methyl 3-[bis(tert-butoxycarbonyl)amino]-6-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)pyrazine-2-carboxylate → Methyl 3-[bis(tert-butoxycarbonyl)amino]-6-(1-tert-butoxycarbonyl-4-piperidyl)pyrazine-2-carboxylate

HRID 1959475Notes

Reaction equation

HRID 1959475 reaction equation
[C:1]([O:5][C:6]([N:8]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C:9]1[C:10]([C:28]([O:30][CH3:31])=[O:29])=[N:11][C:12]([C:15]2[CH2:16][CH2:17][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:19][CH:20]=2)=[CH:13][N:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CO.[Pd]>[C:35]([O:34][C:32]([N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C:9]1[C:10]([C:28]([O:30][CH3:31])=[O:29])=[N:11][C:12]([CH:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:26])([CH3:27])[CH3:25])=[O:22])[CH2:17][CH2:16]2)=[CH:13][N:14]=1)=[O:33])([CH3:36])([CH3:37])[CH3:38]

Participants

4

Reactant 1

HCID 66745644methyl 3-[bis(tert-butoxycarbonyl)amino]-6-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)pyrazine-2-carboxylate

Product 1

HCID 66744506Methyl 3-[bis(tert-butoxycarbonyl)amino]-6-(1-tert-butoxycarbonyl-4-piperidyl)pyrazine-2-carboxylateYield 40.9%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A solution of methyl 3-[bis(tert-butoxycarbonyl)amino]-6-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)pyrazine-2-carboxylate (700 mg, 1.3 mmol) in methanol (28 mL) was stirred with 10% Pd/C (wet) (557 mg, 0.26 mmol) at 35° C. under an atmosphere of hydrogen for 16 h. The reaction mixture was filtered, concentrated in vacuo, and purified via silica gel column chromatography using 10-70% ethyl acetate/hexane to provide methyl 3-[bis(tert-butoxycarbonyl)amino]-6-(1-tert-butoxycarbonyl-4-piperidyl)pyrazine-2-carboxylate (285 mg) as an light orange sticky solid. 1H NMR (400 MHz, CDCl3) δ 8.52 (s, 1H), 4.28 (bs, 2H), 3.97 (s, 3H), 3.06 (t, J=12.0 Hz, 1H), 2.86 (t, J=12.0 Hz, 2H), 1.98 (d, J=12.5 Hz, 2H), 1.79 (qd, J=12.6, 3.9 Hz, 2H), 1.48 (s, 9H), 1.41 (s, 18H). LC/MS m/z 537.7 [M+H]+.

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationconcentrated in vacuo
  3. custompurified via silica gel column chromatography

Sources & evidence

ORD record
ord-ccbbf928e82b48f9886221da92b6efff
Source dataset
uspto-grants-2013_04
Patent number
US08410112B2

Reaction notes

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