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 2364075노트

반응식

HRID 2364075 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][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

참가 물질

8

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 118294042-FluorocyclohexanoneHCID 667430133-amino-5-(5-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide

생성물 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)-one수율 55.1%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 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 (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:

후처리

  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)

출처 및 근거

ORD 기록
ord-7b12ce43a5254864a21702d252d68030
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08691828B2

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