Triethylamine → (Azetidin-1-yl)(5-chloropyrazin-2-yl)methanone

HRID 1990199Notes

Reaction equation

HRID 1990199 reaction equation
C(Cl)(=O)C(Cl)=O.[Cl:7][C:8]1[N:9]=[CH:10][C:11]([C:14]([OH:16])=O)=[N:12][CH:13]=1.[NH:17]1[CH2:20][CH2:19][CH2:18]1.C(N(CC)CC)C>CN(C=O)C.C(Cl)Cl>[N:17]1([C:14]([C:11]2[CH:10]=[N:9][C:8]([Cl:7])=[CH:13][N:12]=2)=[O:16])[CH2:20][CH2:19][CH2:18]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10422AzetidineHCID 65578Oxalyl chlorideHCID 4654725-Chloropyrazinoic acid

Product 1

HCID 46870328(Azetidin-1-yl)(5-chloropyrazin-2-yl)methanoneYield 82.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Oxalyl chloride (1.55 mL, 17.48 mmol), followed by DMF (2 drops), was added to a mixture of 5-chloropyrazine-2-carboxylic acid (2.31 g, 14.57 mmol) in DCM (40 mL). The reaction was stirred at RT for 2 hours after which time the volatiles were removed in vacuo. The residue was taken up DCM (40 mL) and azetidine (1.08 mL, 16.03 mmol) and triethylamine (4.46 mL, 32.06 mmol) added. The mixture was stirred at RT for 72 hours. The volatiles were removed in vacuo and ethyl acetate (100 mL) added to the residue. The organics were washed with water (100 mL), citric acid (50 mL), saturated sodium bicarbonate solution (50 mL), brine (50 mL), dried (MgSO4), filtered and the solvent removed in vacuo to give a yellow solid. The residue was chromatographed on silica, eluting with a gradient of 50-100% ethyl acetate in iso-hexane, to give the desired compound as a yellow solid (2.38 g). 1H NMR δ (CDCl3): 2.35-2.42 (2H, m), 4.26 (2H, t), 4.67 (2H, t), 8.52 (1H, d), 9.09 (1H, d); m/z 198 (M+H)+.

Workup

  1. customwere removed in vacuo
  2. additionadded
  3. stirringThe mixture was stirred at RT for 72 hours
  4. customThe volatiles were removed in vacuo and ethyl acetate (100 mL)
  5. additionadded to the residue
  6. washThe organics were washed with water (100 mL), citric acid (50 mL), saturated sodium bicarbonate solution (50 mL), brine (50 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customthe solvent removed in vacuo
  10. customto give a yellow solid
  11. customThe residue was chromatographed on silica
  12. washeluting with a gradient of 50-100% ethyl acetate in iso-hexane

Sources & evidence

ORD record
ord-c85e8093bebd41e78eb2887e2c4b0835
Source dataset
uspto-grants-2010_01
Patent number
US07642259B2

Reaction notes

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