Methanol → 7-Chloro-2,4-dioxo-3-(2-pyridyl)-1,2,3,4-tetrahydroquinoline

HRID 326283Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 326283
[Cl:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8]C)=O)=[C:4]([NH:12]C(=O)CC2C=NC=CC=2)[CH:3]=1.C[Si](C)(C)[N-:24][Si](C)(C)C.[K+].[C:32]1(C)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.[CH3:39][OH:40]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:5]([C:6](=[O:8])[CH:32]([C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][N:24]=3)[C:39](=[O:40])[NH:12]2)=[CH:10][CH:11]=1

Komponenten

6

Edukt 4

HCID 887MethanolHCID 1140TolueneHCID 3251421Potassium bis(trimethylsilyl)amideHCID 19736673Methyl 4-chloro-2-(3-pyridyl)acetamidobenzoate

Produkt 1

HCID 197366367-Chloro-2,4-dioxo-3-(2-pyridyl)-1,2,3,4-tetrahydroquinoline

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of methyl 2-amino-4-chlorobenzoate (2 g, 10.8 mmol) in 1,2-dichlorethane (60 ml) was added 2-pyridylacetic acid hydrochloride (1.9 g, 10.8 mmol), triethylamine (3.2 ml, 22.7 mmol) and bis (2-oxo-3-oxazolidinyl)phosphinic chloride and the reaction refluxed for 8 h. More 2-pyridylacetic acid (1.9 g, 10.8 mmol) and triethylamine (3.2 ml, 22.7 mmol) were added and refluxing continued for a further 16 h. The solvent was evaporated and the residue partitioned between saturated aqueous sodium bicarbonate solution (50 ml) and dichloromethane (50 ml). The organic phase was dried (MgSO4) and evaporated. The residue was purified by flash chromatography on silica (eluting with 50% ethyl acetate/60°-90° petrol) to afford methyl 4-chloro-2-(3-pyridyl)acetamidobenzoate as a green solid (2.5 g), m.p. 85°-87° C. To a solution of the foregoing amide (1 g, 3.3 mmol) in tetrahydrofuran (40 mml) was added a solution of potassium hexamethyldisilazide in toluene (0.5M, 16.6 ml, 8.3 mmol) and the reaction stirred for 2 h. Methanol (15 ml) was added and the solvent evaporated. The residue was partitioned between aqueous sodium hydroxide (1M, 40 ml) and diethyl ether (40 ml), and the aqueous layer acidified with hydrochloric acid (5M). The resultant precipitate was collected and recrystallised from dimethylformamide/water to afford the title compound as a yellow-green solid; m.p.>330° C. (from DMF/H2O) (Found: C, 61.48; H, 3.20; N, 10.20; C14H9ClN2O2 requires C, 61.66; H, 3.33; N, 10.27%); δH (DMSO-d6) 7.15 (1H, dd, J=8.5 Hz and 1.9 Hz, 5-H), 7.26 (1H, s, 8-H), 7.42 (1H, t, J=6.1 Hz, 5'-H), 8.02 (1H, d, J=8.5 Hz, 5-H), 8.16 (1H, t, J=7.3 Hz, 4'-H), 8.78 (1H, d, J=8.6 Hz, 6'-H), 9.38 (1H, d, J=8.8 Hz, 3'-H), 11.20 (1H, s, NH); m/z 272 (M+).

Aufarbeitung

  1. customthe solvent evaporated
  2. customThe residue was partitioned between aqueous sodium hydroxide (1M, 40 ml) and diethyl ether (40 ml)
  3. customThe resultant precipitate was collected
  4. customrecrystallised from dimethylformamide/water

Quellen und Nachweise

ORD-Eintrag
ord-b278868f4d5d46699341ab35f8516067
Quelldatensatz
uspto-grants-1993_12
Patentnummer
US05268378

Notizen zur Reaktion

Wird geladen…