2-chloro-N-methoxy-N-methylpyrimidine-4-carboxamide → (2-Chloropyrimidin-4-yl)(cyclopropyl)methanone

HRID 1039925Notes

Reaction equation

HRID 1039925 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8](N(OC)C)=[O:9])[CH:5]=[CH:4][N:3]=1.[CH:14]1([Mg]Br)[CH2:16][CH2:15]1>C1COCC1.CCOC(C)=O>[Cl:1][C:2]1[N:7]=[C:6]([C:8]([CH:14]2[CH2:16][CH2:15]2)=[O:9])[CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 2

HCID 772313502-chloro-N-methoxy-N-methylpyrimidine-4-carboxamideHCID 178418630HCID 178418630, compound

Product 1

HCID 77231065(2-Chloropyrimidin-4-yl)(cyclopropyl)methanoneYield 45%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-chloro-N-methoxy-N-methylpyrimidine-4-carboxamide (893 mg, 4.43 mmol) in THF (9 mL) at −78° C. under nitrogen atmosphere was added cyclopropyl magnesium bromide (0.5 M in THF, 13.3 mL, 6.64 mmol) dropwise. The solution was warmed to 0° C. and stirred for an additional 30 min. The solution was diluted with EtOAc, washed with brine, dried with MgSO4, filtered, and concentrated to dryness. Purification on silica gel by flash chromatography (0-100% EtOAc/hexanes) afforded (2-chloropyrimidin-4-yl)(cyclopropyl)methanone (360 mg, 1.97 mmol, 45% yield) as a colorless oil. MS ESI: [M+H]+ m/z 183.1. 1H NMR (500 MHz, CDCl3) δ 8.85 (d, J=4.9, 1H); 7.82 (d, J=4.9, 1H), 3.45-3.31 (m, 1H), 1.30 (m, 2H), 1.22 (m, 2H).

Workup

  1. washwashed with brine
  2. dry with materialdried with MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated to dryness
  5. customPurification on silica gel by flash chromatography (0-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-5fcf1563d16944938dac75c81cdca31e
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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