Sodium hydride → 3-[2-(2-Tert-butoxycarbonylmethyl-1-cyclohexenyl)-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine

HRID 276950

Reaktionsgleichung

Reaktionsgleichung von HRID 276950
[H-].[Na+].C(OP([CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])(OCC)=O)C.O=[C:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH:21]1[N:26]1[C:31](=[O:32])[CH:30]=[CH:29][C:28]([C:33]2[C:34]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)=[N:35][N:36]3[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=23)=[N:27]1>C1(C)C=CC=CC=1>[C:15]([O:14][C:12]([CH2:11][C:20]1[CH2:25][CH2:24][CH2:23][CH2:22][C:21]=1[N:26]1[C:31](=[O:32])[CH:30]=[CH:29][C:28]([C:33]2[C:34]([C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=3)=[N:35][N:36]3[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=23)=[N:27]1)=[O:13])([CH3:16])([CH3:17])[CH3:18].[C:15]([O:14][C:12]([CH2:11][C:20]1[CH:21]([N:26]2[C:31](=[O:32])[CH:30]=[CH:29][C:28]([C:33]3[C:34]([C:42]4[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=4)=[N:35][N:36]4[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=34)=[N:27]2)[CH2:22][CH2:23][CH2:24][CH:25]=1)=[O:13])([CH3:16])([CH3:17])[CH3:18].[C:15]([O:14][C:12](/[CH:11]=[C:20]1/[CH:21]([N:26]2[C:31](=[O:32])[CH:30]=[CH:29][C:28]([C:33]3[C:34]([C:42]4[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=4)=[N:35][N:36]4[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=34)=[N:27]2)[CH2:22][CH2:23][CH2:24][CH2:25]/1)=[O:13])([CH3:16])([CH3:17])[CH3:18]

Komponenten

7

Edukt 3

HCID 24758Sodium hydrideHCID 2773685tert-Butyl diethylphosphonoacetateHCID 110690413-[2-(2-Oxocyclohexyl)-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine

Produkt 3

HCID 111136373-[2-(2-Tert-butoxycarbonylmethyl-1-cyclohexenyl)-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridineHCID 15870061(E)-3-[2-{2-(tert-butoxycarbonylmethylene)cyclohexyl}-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridineHCID 158700623-[2-{2-(Tert-butoxycarbonylmethyl)-2-cyclohexen-1-yl}-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Versuchsvorschrift

To a suspension of sodium hydride (44.2 g, 60% oil) in toluene (5.6 l) was added carefully tert-butyl (diethoxyphosphoryl)acetate (278.3 g) at 0° C. under nitrogen atmosphere. After being stirred for 30 minutes, to a reaction mixture was added by portions 3-[2-(2-oxocyclohexyl)-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine (282.7 g), and which was stirred for additional 68 hours at ambient temperature. A reaction mixture was poured into ice-water (3 l) and organic layer was separated. Aqueous layer was reextracted with ethyl acetate (2 l). Organic layer was combined, washed In turn with water (2 l×3) and saturated sodium chloride in water, and dried over magnesium sulfate. Evaporation of the solvent gave a residue, which was chromatographed on silica gel (270-400 mesh, 7 Kg) eluting in turn with 9%, 17% and 33% ethyl acetate in toluene. Fractions containing another isomer were further purified under the same conditions (silica gel 1 kg). Fractions containing each of desired products were collected and concentrated in vacuo to give 3-[2-{2-(tert-butoxycarbonylmethyl)-1-cyclohexenyl}-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo-[1,5-a]pyridine (252.9 g), 3-[2-{2-(tert-butoxycarbonylmethyl)-2-cyclohexen-1-yl}-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine (31.68 g) and (E)-3-[2-{2-(tert-butoxycarbonylmethylene)cyclohexyl}-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine (16.08 g) respectively.

Aufarbeitung

  1. stirringwas stirred for additional 68 hours at ambient temperature
  2. customwas separated
  3. washwashed In turn with water (2 l×3) and saturated sodium chloride in water
  4. dry with materialdried over magnesium sulfate
  5. customEvaporation of the solvent
  6. customgave a residue, which
  7. customwas chromatographed on silica gel (270-400 mesh, 7 Kg)
  8. washeluting in turn with 9%, 17% and 33% ethyl acetate in toluene
  9. additionFractions containing another isomer
  10. customwere further purified under the same conditions (silica gel 1 kg)
  11. additionFractions containing each of desired products
  12. customwere collected
  13. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-8733843503f34f8bb3f9f8a8b99bcaf2
Quelldatensatz
uspto-grants-2002_03
Patentnummer
US06355640B1

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