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

HRID 1748410노트

반응식

HRID 1748410 반응식
[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

참가 물질

8

반응물 4

HCID 99743-Fluorobenzyl chlorideHCID 10796Cesium carbonateHCID 90417603Ethyl 7-((3-fluorobenzyl)oxy)-1,5-naphthyridine-3-carboxylateHCID 136227102Ethyl 7-hydroxy-1,5-naphthyridine-3-carboxylate2회

생성물 1

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

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-9c4c19607e6f403386a7b72297c4657d
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09150572B2

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