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

HRID 2364094Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2364094
[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][C:17]1([F:24])[CH2:22][CH2:21][C:20](=O)[CH2:19][CH2:18]1.CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=O.[O-]S([O-])(=O)=O.[Mg+2].C([O-])(O)=O.[Na+]>CC(N(C)C)=O>[F:16][C:17]1([F:24])[CH2:22][CH2:21][C:20]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)[CH2:19][CH2:18]1

Komponenten

7

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 157890924,4-DifluorocyclohexanoneHCID 667430133-amino-5-(5-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide

Produkt 1

HCID 667442354,4-difluoro-6'-(5-methyl-1H-pyrazol-4-yl)-1'H-spiro[cyclohexane-1,2'-thieno[3,2-d]pyrimidin]-4'(3'H)-oneAusbeute 39 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of 3-amino-5-(5-methyl-1H-pyrazol-4-yl) thiophene-2-carboxamide (100 mg, 0.45 mmol), 4,4-difluorocyclohexanone (181 mg, 1.35 mmol), CSA (10 mg, 0.045 mmol), MgSO4 (108 mg, 0.90 mmol) and DMA (1 mL) was stirred at 80° C. for 2 h. The mixture was poured into saturated aqueous NaHCO3. The organic materials were extracted with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, 90:10 hexane/EtOAc to EtOAc), then crystallized from MeOH/EtOAc to give the title compound (59 mg, 39%) as a pale yellow solid:

Aufarbeitung

  1. extractionThe organic materials were extracted with EtOAc
  2. washThe combined extracts were washed with water and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customAfter removal of the solvent at reduced pressure
  6. customthe residue was purified by column chromatography (Purif, silica gel, 90:10 hexane/EtOAc to EtOAc)
  7. customcrystallized from MeOH/EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-8469ed7e390d4222815ee5b85d582cdb
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08691828B2

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