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

HRID 1893648Notes

Reaction equation

HRID 1893648 reaction equation
[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]

Participants

8

Reactant 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, compoundHCID 86632794HCID 86632794, compound

Product 1

HCID 76604970HCID 76604970, compoundYield 39.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-0fc8d53417574b809723d823b87968d4
Source dataset
uspto-grants-2013_08
Patent number
US08513186B2

Reaction notes

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