1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Methyl 1-(4-fluorobenzyl)-2-oxo-1,2-dihydropyridine-3-carboxylate

HRID 347542

Reaction equation

HRID 347542 reaction equation
O=[C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=[CH:4][O:3]1.[F:12][C:13]1[CH:20]=[CH:19][C:16]([CH2:17][NH2:18])=[CH:15][CH:14]=1.CCN=C=NCCCN(C)C>CN(C=O)C.CN(C1C=CN=CC=1)C>[F:12][C:13]1[CH:20]=[CH:19][C:16]([CH2:17][N:18]2[CH:4]=[CH:5][CH:6]=[C:7]([C:8]([O:10][CH3:11])=[O:9])[C:2]2=[O:3])=[CH:15][CH:14]=1

Participants

6

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 673264-FluorobenzylamineHCID 117704Methyl 2-oxo-2H-pyran-3-carboxylate

Product 1

HCID 21081722Methyl 1-(4-fluorobenzyl)-2-oxo-1,2-dihydropyridine-3-carboxylateYield 73.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

A heterogeneous mixture of methyl 2-oxo-2H-pyran-3-carboxylate (2.0 g, 13 mmol, 1.0 eq, Aldrich) and 4-fluorobenzylamine (1.5 mL, 13 mmol, 1.0 eq) in DMF (10 mL) was stirred at room temperature for 3 h. The reaction mixture was treated with EDCI (3.4 g, 18 mmol, 1.4 eq) and DMAP (0.11 g, 9.91 mmol, 0.07 eq) at room temperature and the resulting solution was stirred for 12 h. The reaction mixture was quenched with 1 N aqueous HCl and the solution was extracted with ethyl acetate (4×50 mL). The combined organic extracts were washed with 10% aqueous LiCl (3×70 mL), dried (Na2SO4), filtered and the filtrate concentrated in vacuo to afford the product (2.5 g, 73%) as a solid, which was used without further purification. 1H NMR (DMSO-d6) δ 8.17–8.20 (m, 1H), 8.03–8.05 (m, 1H), 7.38–7.46 (m, 2H), 7.16–7.22 (m, 2H), 6.37 (dd, 1H, J=6.94 Hz), 5.13 (s, 2H), 3.73 (s, 3H); HRMS(ESI): calcd.: 262.0879, found: 262.0885.

Workup

  1. stirringthe resulting solution was stirred for 12 h
  2. customThe reaction mixture was quenched with 1 N aqueous HCl
  3. extractionthe solution was extracted with ethyl acetate (4×50 mL)
  4. washThe combined organic extracts were washed with 10% aqueous LiCl (3×70 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated in vacuo

Sources & evidence

ORD record
ord-606731b10f1b43a985c14dd093935f6a
Source dataset
uspto-grants-2007_02
Patent number
US07173031B2

Linked notes

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