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

HRID 2183786Notes

Reaction equation

HRID 2183786 reaction equation
[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

Participants

7

Reactant 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, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

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.

Workup

  1. customfreshly prepared
  2. temperatureThe reaction mixture was cooled to −30° 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

Sources & evidence

ORD record
ord-ad0f3a58675340b5856d2ebe3ba76776
Source dataset
uspto-grants-2005_05
Patent number
US06900205B2

Reaction notes

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