1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 76604970、化合物

HRID 2405798ノート

反応式

HRID 2405798 の反応式
[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]

参加物

8

反応物 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、化合物HCID 86632794HCID 86632794、化合物

生成物 1

HCID 76604970HCID 76604970、化合物収率 39.3%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-5fced3a75c6740efbfb9987c0e51b285
出典データセット
uspto-grants-2014_08
特許番号
US08809267B2

反応ノート

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