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 2364094노트

반응식

HRID 2364094 반응식
[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

참가 물질

7

반응물 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

생성물 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)-one수율 39%

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

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온도
80 °C

실험 절차

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:

후처리

  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

출처 및 근거

ORD 기록
ord-8469ed7e390d4222815ee5b85d582cdb
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08691828B2

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