2-Chloropyrimidine → HCID 21475314, compound

HRID 2264417Notes

Reaction equation

HRID 2264417 reaction equation
Cl[C:2]1[N:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[CH2:8]([O:10][C:11]([N:13]1[CH2:18][CH2:17][CH:16]([NH2:19])[CH2:15][CH2:14]1)=[O:12])[CH3:9]>CC(N(C)C)=O.C(N(CC)CC)C.[Cu]Br>[CH2:8]([O:10][C:11]([N:13]1[CH2:14][CH2:15][CH:16]([NH:19][C:2]2[N:7]=[CH:6][CH:5]=[CH:4][N:3]=2)[CH2:17][CH2:18]1)=[O:12])[CH3:9]

Participants

6

Reactant 2

HCID 744042-ChloropyrimidineHCID 100867Ethyl 4-amino-1-piperidinecarboxylate

Product 1

HCID 21475314HCID 21475314, compound

Reagents, catalysts & solvents 3

HCID 24593copper(I) bromideCatalystHCID 8471TriethylamineSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
200 °C

Procedure

A mixture of 2-chloro-pyrimidine (2.00 g, 17.46 mmol, 1.0 equiv), 4-amino-piperidine-1-carboxylic acid ethyl ester (3.61 g, 20.95 mmol, 1.2 equiv) and copper(I) bromide (0.25 g, 1.75 mmol, 0.1 equiv) in anhydrous DMAc (5 mL) and triethylamine (5 mL) was heated by microwave irradiation to 200° C. for 20 min. The organic phase was concentrated under reduced pressure and the residue extracted with ethyl acetate (3×50 mL). The combined organic phases were dried over MgSO4 and the product purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of dichloromethane (+1% triethylamine)/methanol providing 1.07 g (25%) of the title compound. MS (ISP): 251.4 [M+H]+.

Workup

  1. concentrationThe organic phase was concentrated under reduced pressure
  2. extractionthe residue extracted with ethyl acetate (3×50 mL)
  3. dry with materialThe combined organic phases were dried over MgSO4
  4. customthe product purified by silica column chromatography
  5. washeluting with a gradient of dichloromethane (+1% triethylamine)/methanol providing 1.07 g (25%) of the title compound

Sources & evidence

ORD record
ord-97ed1c6f334e4bcdbf38355f673f1077
Source dataset
uspto-grants-2010_12
Patent number
US07855194B2

Reaction notes

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