Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → 2-fluoro-6'-(5-methyl-1H-pyrazol-4-yl)-1'H-spiro [cyclohexane-1,2'-thieno[3,2-d]pyrimidin]-4'(3'H)-one

HRID 2364075Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2364075
[NH2:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[N:9][NH:10][C:11]=2[CH3:12])[S:4][C:3]=1[C:13]([NH2:15])=[O:14].[F:16][CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][C:18]1=O.CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=O.[O-]S([O-])(=O)=O.[Mg+2].C([O-])(O)=O.[Na+]>CCOC(C)=O.CC(N(C)C)=O>[F:16][CH:17]1[C:22]2([NH:1][C:2]3[CH:6]=[C:5]([C:7]4[CH:8]=[N:9][NH:10][C:11]=4[CH3:12])[S:4][C:3]=3[C:13](=[O:14])[NH:15]2)[CH2:21][CH2:20][CH2:19][CH2:18]1

Komponenten

8

Edukt 5

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 24083Sulfuric acid magnesium salt (1:1)HCID 516892Sodium BicarbonateHCID 118294042-FluorocyclohexanoneHCID 667430133-amino-5-(5-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide

Produkt 1

HCID 468982472-fluoro-6'-(5-methyl-1H-pyrazol-4-yl)-1'H-spiro [cyclohexane-1,2'-thieno[3,2-d]pyrimidin]-4'(3'H)-oneAusbeute 55,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8857Ethyl AcetateLösungsmittelHCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of 3-amino-5-(5-methyl-1H-pyrazol-4-yl)thiophene -2-carboxamide (66 mg, 0.30 mmol), 2-fluorocyclohexanone (0.10 mL, 0.90 mmol), CSA (7.0 mg, 0.030 mmol), MgSO4 (72 mg, 0.60 mmol) and DMA (1 mL) was stirred at 80° C. for 2 h. Then, saturated aqueous NaHCO3 and EtOAc were added to quench the reaction. The organic materials were extracted with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel 85:15 hexane/EtOAc to EtOAc), then crystallized from MeOH/EtOAc/hexane) to give the title compound (53 mg, 55%) as a pale yellow solid:

Aufarbeitung

  1. customto quench
  2. customthe reaction
  3. extractionThe organic materials were extracted with EtOAc
  4. washThe combined extracts were washed with water and brine
  5. dry with materialdried over Na2SO4
  6. customAfter removal of the solvent at reduced pressure
  7. customthe residue was purified by column chromatography (Purif, silica gel 85:15 hexane/EtOAc to EtOAc)
  8. customcrystallized from MeOH/EtOAc/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-7b12ce43a5254864a21702d252d68030
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08691828B2

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