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Hydrochloric Acid → 6'-(5-methyl-1H-pyrazol-4-yl)-1'H-spiro [cyclohexane-1,2'-thieno[3,2-d]pyrimidin]-4'(3'H)-one

HRID 2364034
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HRID 2364034 반응식
[CH3:1][C:2]1([CH3:18])[NH:7][C:6]2[CH:8]=[C:9]([C:11]3[CH:12]=[N:13][NH:14][C:15]=3[CH3:16])[S:10][C:5]=2[C:4](=[O:17])[NH:3]1.Cl.C([O-])(O)=O.[Na+].[C:25]1(=O)[CH2:30]CCC[CH2:26]1.[O-]S([O-])(=O)=O.[Mg+2].CC1C=CC(S(O)(=O)=O)=CC=1>CN(C=O)C.CO>[CH3:16][C:15]1[NH:14][N:13]=[CH:12][C:11]=1[C:9]1[S:10][C:5]2[C:4](=[O:17])[NH:3][C:2]3([CH2:18][CH2:30][CH2:25][CH2:26][CH2:1]3)[NH:7][C:6]=2[CH:8]=1
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참가 물질

9

반응물 6

HCID 313Hydrochloric AcidHCID 6101p-Toluenesulfonic acidHCID 7967CyclohexanoneHCID 24083Sulfuric acid magnesium salt (1:1)HCID 516892Sodium Bicarbonate2회HCID 66743505Cdc7-IN-15

생성물 1

HCID 66743431
6'-(5-methyl-1H-pyrazol-4-yl)-1'H-spiro [cyclohexane-1,2'-thieno[3,2-d]pyrimidin]-4'(3'H)-one
수율 41.3%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6228Dimethylformamide용매

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온도
50 °C

실험 절차

A mixture of 2,2-dimethyl-6-(5-methyl-1H-pyrazol-4-yl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one (0.090 g, 0.343 mmol), 1 M HCl (1.2 mL, 1.2 mmol) and MeOH (4 mL) was stirred at 50° C. for 2 h. Then, the reaction mixture was poured into excess saturated aqueous NaHCO3 and extracted with EtOAc, and the extract was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was mixed with cyclohexanone (2 mL, 19.3 mmol), MgSO4 (0.041 g, 0.343 mmol), PTSA (3.3 mg, 0.017 mmol) and DMF (2 mL). The mixture was stirred at 80° C. for 3 h. The mixture was poured into saturated aqueous NaHCO3 and extracted with EtOAc, and the extract was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc then to 90:10 EtOAc/MeOH). The obtained oil was purified again by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc) to give a yellow solid. This solid was triturated with EtOAc/hexane and collected by filtration to afford the title compound (42.8 mg, 41%) as a yellow solid:

후처리

  1. extractionextracted with EtOAc
  2. dry with materialthe extract was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. stirringThe mixture was stirred at 80° C. for 3 h
  6. extractionextracted with EtOAc
  7. dry with materialthe extract was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc
  11. customThe obtained oil was purified again by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc)
  12. customto give a yellow solid
  13. customThis solid was triturated with EtOAc/hexane
  14. filtrationcollected by filtration

출처 및 근거

ORD 기록
ord-01c7d3d0bdcb466c8799809109955355
출처 데이터셋
uspto-grants-2014_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08691828B2

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