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

HRID 2364093
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HRID 2364093 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].O=[C:17]1[CH2:22][CH2:21][CH:20]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:19][CH2:18]1.[O-]S([O-])(=O)=O.[Mg+2].CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=O.C([O-])(O)=O.[Na+]>CCCCCC.CO.CCOC(C)=O.CC(N(C)C)=O>[CH3:12][C:11]1[NH:10][N:9]=[CH:8][C:7]=1[C:5]1[S:4][C:3]2[C:13](=[O:14])[NH:15][C:17]3([CH2:18][CH2:19][CH:20]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:28])([CH3:27])[CH3:29])[CH2:21][CH2:22]3)[NH:1][C:2]=2[CH:6]=1
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참가 물질

9

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 1512535tert-butyl N-(4-oxocyclohexyl)carbamateHCID 667430133-amino-5-(5-methyl-1H-pyrazol-4-yl)thiophene-2-carboxamide

생성물 1

HCID 68074185
tert-butyl [6'-(5-methyl-1H-pyrazol-4-yl)-4'-oxo-3',4'-dihydro-1'H-spiro[cyclohexane-1,2'-thieno[3,2-d]pyrimidin]-4-yl]carbamate

시약·촉매·용매 3

HCID 8058Hexane용매HCID 31374Dimethylacetamide용매HCID 21584119Ethylacetate methanol용매

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온도
100 °C

실험 절차

A mixture of 3-amino-5-(5-methyl-1H-pyrazol-4-yl) thiophene-2-carboxamide (111 mg, 0.50 mmol), tert-butyl (4-oxocyclohexyl)carbamate (320 mg, 1.50 mmol), MgSO4 (120 mg, 1.00 mmol), CSA (11.6 mg, 0.05 mmol) and DMA (3 mL) was stirred at 100° C. for 1 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, hexane to EtOAc then to 80:20 EtOAc/MeOH). The residue obtained was dissolved with small amount of MeOH/EtOAc and added dropwise to a stirred solution of hexane (100 mL). The precipitate was collected by filtration to afford the title compound (122 mg, 58%, a mixture of 11:9 cis/trans isomers, absolute structure not determined) as yellow solid:

후처리

  1. extractionextracted with EtOAc
  2. dry with materialthe extract was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by column chromatography (Purif, silica gel, hexane to EtOAc
  6. customThe residue obtained
  7. filtrationThe precipitate was collected by filtration

출처 및 근거

ORD 기록
ord-a18a7a35cc91476dbfff8185b58e21a8
출처 데이터셋
uspto-grants-2014_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08691828B2

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