Propanal → 2-anilino-7-chloro-6-fluoro-5-(1-hydroxypropyl)-1-phenyl-1,8-naphthyridin-4(1H)-one

HRID 2215006노트

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HRID 2215006 반응식
[NH:1]([C:8]1[N:9]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:10]2[C:15]([C:16](=[O:18])[CH:17]=1)=[CH:14][C:13]([F:19])=[C:12]([Cl:20])[N:11]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]N1C(C)(C)CCCC1(C)C.CC1(C)CCCC(C)(C)N1.[Li]CCCC.[CH:53](=[O:56])[CH2:54][CH3:55]>C1COCC1>[NH:1]([C:8]1[N:9]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:10]2[C:15]([C:16](=[O:18])[CH:17]=1)=[C:14]([CH:53]([OH:56])[CH2:54][CH3:55])[C:13]([F:19])=[C:12]([Cl:20])[N:11]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

7

반응물 5

HCID 527PropanalHCID 130352,2,6,6-TetramethylpiperidineHCID 219481862-anilino-7-chloro-6-fluoro-1-phenyl-1,8-naphthyridin-4(1H)-oneHCID 178418339ButyllithiumHCID 178418821HCID 178418821, 화합물

생성물 1

HCID 219481892-anilino-7-chloro-6-fluoro-5-(1-hydroxypropyl)-1-phenyl-1,8-naphthyridin-4(1H)-one수율 103.3%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
-30 °C

실험 절차

A −40° C. solution of 2-anilino-7-chloro-6-fluoro-1-phenyl-1,8-naphthyridin-4(1H)-one (100 mg, 0.274 mmol) in THF (10 mL) was treated with LTMP (1.10 mmol, freshly prepared by mixing 2,2,6,6-Tetramethyl piperidine and n-BuLi at 0° C. for 30 min.). The mixture was then allowed to warm to 0  C. for 2 h. The reaction mixture was cooled to −30° C. and propionaldehyde (159 mg, 2.74 mmol) was added. The reaction was stirred at −30° C. for 2 h before it was slowly quenched with saturated aqueous NH4Cl. The mixture was extracted with EtOAc and the organic layer was dried over MgSO4 and concentrated in vacuo. The residue was purified by silica gel flash chromatography to afford 2-anilino-7-chloro-6-fluoro-5-(1-hydroxypropyl)-1-phenyl-1,8-naphthyridin-4(1H)-one (120 mg, 97%) as a white solid: LCMS RT: 3.14 min, MH+: 424.2. Other electrophiles such as disulfide may be used to quench the anion.

후처리

  1. customfreshly prepared
  2. temperatureto warm to 0  C
  3. customwas slowly quenched with saturated aqueous NH4Cl
  4. extractionThe mixture was extracted with EtOAc
  5. dry with materialthe organic layer was dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel flash chromatography

출처 및 근거

ORD 기록
ord-d7dce3b0d2db4b8fa63a8eb1c9983b25
출처 데이터셋
uspto-grants-2006_09
특허 번호
US07109196B2

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