Methyl 2,4-dichloropyrimidine-6-carboxylate → HCID 86618543, compound

HRID 2242972Notes

Reaction equation

HRID 2242972 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[C:9](Cl)[N:8]=[C:7]([Cl:12])[N:6]=1)=[O:4].[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([NH2:26])[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14]>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[C:9]([NH:26][CH:23]2[CH2:22][CH2:21][N:20]([C:18]([O:17][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:19])[CH2:25][CH2:24]2)[N:8]=[C:7]([Cl:12])[N:6]=1)=[O:4]

Participants

4

Reactant 2

HCID 239689Methyl 2,4-dichloropyrimidine-6-carboxylateHCID 12682914-Amino-1-Boc-piperidine

Product 1

HCID 86618543HCID 86618543, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2,6-dichloro-pyrimidine-4-carboxylic acid methyl ester (3.98 g, 19.19 mmol, 1.0 equiv; commercially available) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (5.0 g, 24.94 mmol, 1.3 equiv) in anhydrous DMF (100 mL) was heated to 60° C. for 18 h. The organic phase was concentrated under reduced pressure and the crude reaction mixture extracted from a 1 M NaOH (100 mL) solution with ethyl acetate (3×50 mL). The combined organic phases were dried over MgSO4 and the product purified with silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane/ethyl acetate providing 3.46 g (49%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 1.42-1.51 (m, 2H), 1.47 (s, 9H), 2.00-2.05 (m, 2H), 2.90-3.01 (m, 2H), 3.92 (s, 3H), 4.05-4.10 (m, 2H), 4.19 (br s, 1H), 7.10 (s, 1H), 7.17 (br s, 1H). 13C NMR (75 MHz, CDCl3): δ28.30, 31.23, 42.41, 48.00, 52.88, 79.61, 106.38, 153.58, 154.61, 161.21, 163.75, 164.23. MS (ISP): 371.1 [M+H]+.

Workup

  1. concentrationThe organic phase was concentrated under reduced pressure
  2. customthe crude reaction mixture
  3. extractionextracted from a 1 M NaOH (100 mL) solution with ethyl acetate (3×50 mL)
  4. dry with materialThe combined organic phases were dried over MgSO4
  5. customthe product purified with silica column chromatography
  6. washeluting with a gradient of heptane/ethyl acetate providing 3.46 g (49%) of the title compound

Sources & evidence

ORD record
ord-3b4b3b64441647bcbe347353a4f8d405
Source dataset
uspto-grants-2010_03
Patent number
US07674804B2

Reaction notes

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