2-Chloro-4,6-dimethylpyrimidine → HCID 67342807, compound

HRID 451416Notes

Reaction equation

HRID 451416 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[N:3]=1.[NH2:10][CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1.CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>O1CCOCC1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:20]([O:19][C:17]([N:14]1[CH2:15][CH2:16][CH:11]([NH:10][C:2]2[N:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[N:3]=2)[CH2:12][CH2:13]1)=[O:18])([CH3:23])([CH3:21])[CH3:22]

Participants

8

Reactant 4

HCID 205502-Chloro-4,6-dimethylpyrimidineHCID 12682914-Amino-1-Boc-piperidineHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 23676156Sodium t-butoxide

Product 1

HCID 67342807HCID 67342807, compoundYield 51%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

To a mixture of 2-chloro-4,6-dimethylpyrimidine (5.00 g, 0.035 mol), 4-amino-1-Boc-piperidine (7.023 g, 0.035 mol), sodium tert-butoxide (5.055 g, 0.53 mol) in dioxane (120 mL) was added under an argon atmosphere palladium(II) acetate (0.630 g, 0.003 mol) and 2-(dicyclohexylphospino)biphenyl (1.966 g, 0.006 mmol). The reaction mixture was stirred for 5 hours at 130° C. It was diluted with ethyl acetate (400 mL) and washed with aqueous sodium carbonate (1M, 200 mL), water (200 mL) and brine (150 mL). The combined aqueous layers were extracted with ethyl acetate (400 mL) and the combined organic layers were dried over sodium sulfate. Concentration and purification by chromatography (SiO2, n-heptane/ethyl acetate=2:1 to 1:1) afforded the title compound (5.44 g, 51%) as an orange oil.

Workup

  1. washwashed with aqueous sodium carbonate (1M, 200 mL), water (200 mL) and brine (150 mL)
  2. extractionThe combined aqueous layers were extracted with ethyl acetate (400 mL)
  3. dry with materialthe combined organic layers were dried over sodium sulfate
  4. concentrationConcentration and purification by chromatography (SiO2, n-heptane/ethyl acetate=2:1 to 1:1)

Sources & evidence

ORD record
ord-81f8c8205ff546a7bbd54ae354e36f69
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

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