3-Fluorobenzyl chloride → 7-[(3-Fluorophenyl)methoxy]-1,5-naphthyridine-3-carboxamide

HRID 513961Notes

Reaction equation

HRID 513961 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][CH:24]=1)[CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:17](OCC)=[O:18])[CH:13]=[N:14]2)=[N:9][CH:8]=1.OC1C=C2C(C=C(C(OCC)=O)C=N2)=[N:28]C=1.C([O-])([O-])=O.[Cs+].[Cs+].FC1C=C(C=CC=1)CCl>CN(C=O)C.O.CCOC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([CH2:5][O:6][C:7]2[CH:16]=[C:15]3[C:10]([CH:11]=[C:12]([C:17]([NH2:28])=[O:18])[CH:13]=[N:14]3)=[N:9][CH:8]=2)[CH:22]=[CH:23][CH:24]=1

Participants

8

Reactant 4

HCID 99743-Fluorobenzyl chlorideHCID 10796Cesium carbonateHCID 90417603Ethyl 7-((3-fluorobenzyl)oxy)-1,5-naphthyridine-3-carboxylateHCID 136227102Ethyl 7-hydroxy-1,5-naphthyridine-3-carboxylate2×

Product 1

HCID 862964697-[(3-Fluorophenyl)methoxy]-1,5-naphthyridine-3-carboxamideYield 69%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Ethyl 7-((3-fluorobenzyl)oxy)-1,5-naphthyridine-3-carboxylate. To a solution of ethyl 7-hydroxy-1,5-naphthyridine-3-carboxylate (Intermediate 4, 1.0 g, 4.59 mmol) in DMF (20 mL) was added Cs2CO3 (2.2 g, 6.75 mmol), followed by 3-fluorobenzyl chloride (0.6 mL, 5.02 mmol). The reaction was stirred at ambient temperature for 72 h. The crude reaction mixture was poured into EtOAc and water. The aqueous later was extracted with EtOAc and the combined organic fractions were washed with brine and concentrated under reduced pressure onto silica. Purification (FCC, SiO2, 0-60%, EtOAc/hexanes) afforded the title compound as a white solid (1.0 g, 69%). 1H NMR (400 MHz, CDCl3) δ 9.44 (t, J=2.0 Hz, 1H), 9.00-8.94 (m, 1H), 8.88 (t, J=2.3 Hz, 1H), 7.74-7.65 (m, 1H), 7.47-7.33 (m, 1H), 7.28-7.26 (m, 1H), 7.21 (d, J=9.4 Hz, 1H), 7.07 (t, J=8.6 Hz, 1H), 5.25 (s, 2H), 4.59-4.38 (m, 2H), 1.52-1.41 (m, 3H). [M+H]=327.2.

Workup

  1. customThe crude reaction mixture
  2. extractionThe aqueous later was extracted with EtOAc
  3. washthe combined organic fractions were washed with brine
  4. concentrationconcentrated under reduced pressure onto silica
  5. customPurification (FCC, SiO2, 0-60%, EtOAc/hexanes)

Sources & evidence

ORD record
ord-282871b6f7bc47efbcd6b068af00f845
Source dataset
uspto-grants-2015_08
Patent number
US09102674B2

Reaction notes

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