1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 76604970, 화합물

HRID 2405798노트

반응식

HRID 2405798 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([O:13][C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:24][CH3:25])=[CH:21][CH:22]=3)[CH:17]=[CH:16][N:15]=2)[CH2:10][CH:9]1[C:26](=[O:35])[NH:27]C1(C=C)CC1=C=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C([O:43]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH2:69]([C:72]1([O:75][S:76](=[O:79])(=[O:78])[NH2:77])[CH2:74][CH2:73]1)[CH2:70][CH3:71].[CH2:80]1[CH2:90][CH2:89]N2[C:83](=NCCC2)[CH2:82][CH2:81]1>CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([O:13][C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:24][CH3:25])=[CH:21][CH:22]=3)[CH:17]=[CH:16][N:15]=2)[CH2:10][CH:9]1[C:26](=[O:35])[NH:27][C:90]1([C:89]([NH:77][S:76]([O:75][C:72]2([CH2:69][CH2:70][CH3:71])[CH2:73][CH2:74]2)(=[O:78])=[O:79])=[O:43])[CH2:80][CH:81]1[CH:82]=[CH2:83])=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

8

반응물 5

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57785269HCID 57785269, 화합물HCID 86632794HCID 86632794, 화합물

생성물 1

HCID 76604970HCID 76604970, 화합물수율 39.3%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 2-(1-carbonyl-2-vinyl-cyclopropylcarbamoyl)-4-(6-methoxy-isoquinolin-1-yloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.00 g, 2.01 mmol) in DMF (10 mL) was added HATU (1.14 g, 3.02 mmol, 1.5 equiv.) and DIPEA (0.52 mL, 2.98 mmol, 1.5 equiv.). The solution was stirred at room temperature for 15 min before sulfamic acid 1-propyl-cyclopropyl ester (0.71 mg, 4.00 mmol, 2 equiv.) and DBU (1.2 mL, 8.02 mmol, 4 equiv.) were added. The reaction was then stirred for an additional 15 h. The solution was diluted with EtOAc and washed twice with 1M aqueous HCl and Brine. The organic layer was dried over MgSO4 and concentrated in vacuo. The desired sulfamate was precipitated from EtOH/H2O to provide 4-(6-methoxy-isoquinolin-1-yloxy)-2-[1-(1-propyl-cyclopropoxysulfonylaminocarbonyl)-2-vinyl-cyclopropylcarbamoyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (520 mg, 39%). The mother liquor was concentrated in vacuo and further purified by column chromatography (50→100 EtOAc/hexanes) to provide additional sulfamate. Precipitation from EtOH/H2O provided 4-(6-methoxy-isoquinolin-1-yloxy)-2-[1-(1-propyl-cyclopropoxysulfonylaminocarbonyl)-2-vinyl-cyclopropylcarbamoyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (244 mg, 18%): LCMS found 659.0 [M+H]+.

후처리

  1. additionwere added
  2. washwashed twice with 1M aqueous HCl and Brine
  3. dry with materialThe organic layer was dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe desired sulfamate was precipitated from EtOH/H2O

출처 및 근거

ORD 기록
ord-5fced3a75c6740efbfb9987c0e51b285
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08809267B2

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