Toluene → 4-[(3-Methoxy-5-methyl-pyrazin-2-ylamino)-methyl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1827225Notes

Reaction equation

HRID 1827225 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][NH:15][C:16]2[C:21]([O:22][CH3:23])=[N:20][C:19](Br)=[CH:18][N:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:25][Zn]C.C1(C)C=CC=CC=1>O1CCCC1.O.C(OCC)(=O)C.[Ni](Cl)Cl.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][NH:15][C:16]2[C:21]([O:22][CH3:23])=[N:20][C:19]([CH3:25])=[CH:18][N:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 3

HCID 1140TolueneHCID 235773094-[(5-Bromo-3-methoxy-pyrazin-2-ylamino)-methyl]-piperidine-1-carboxylic acid tert-butyl esterHCID 178477796HCID 178477796, compound

Product 1

HCID 235773064-[(3-Methoxy-5-methyl-pyrazin-2-ylamino)-methyl]-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 4

HCID 2724937Dichloro(1,1'-(1,3-propanediyl)bis(1,1-diphenylphosphine-kappaP))nickelCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 4-[(5-bromo-3-methoxy-pyrazin-2-ylamino)-methyl]-piperidine-1-carboxylic acid tert-butyl ester (EXAMPLE 131, STEP 1) (0.20 g, 0.0005 mol) in tetrahydrofuran (1 mL), under nitrogen, was added 1,3-bis(diphenylphosphino)propane nickel(II) chloride (0.034 g, 0.0625 mmol) followed by a dropwise addition of 2.0M dimethylzinc in toluene (0.313 mL, 0.000625 mol). The reaction mixture was stirred for 1.5 h, diluted with water (5 mL) and ethyl acetate (30 mL). The organic layer was removed, dried over sodium sulfate, filtered and concentrated to an oil. The oil was chromatographed on silica using a gradient of 20–50% ethyl acetate/hexane to give the title compound as a foam. M.S.(M+1): 337.

Workup

  1. customThe organic layer was removed
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated to an oil
  5. customThe oil was chromatographed on silica using a gradient of 20–50% ethyl acetate/hexane

Sources & evidence

ORD record
ord-5fa1d2877dbf4e5eb6c083abfca4e866
Source dataset
uspto-grants-2006_05
Patent number
US07053089B2

Reaction notes

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