Cesium carbonate → (S)-3-(tert-Butoxycarbonylamino)-1-[4-(tert-butoxycarbonylamino)-5-isoquinolinesulfonyl]pyrrolidine

HRID 1962433Notes

Reaction equation

HRID 1962433 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][CH2:12][N:11]([S:14]([C:17]2[C:18]3[C:19](Br)=[CH:20][N:21]=[CH:22][C:23]=3[CH:24]=[CH:25][CH:26]=2)(=[O:16])=[O:15])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:74](=[O:81])([O:76][C:77]([CH3:80])([CH3:79])[CH3:78])[NH2:75].C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C>[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][CH2:12][N:11]([S:14]([C:17]2[C:18]3[C:19]([NH:75][C:74]([O:76][C:77]([CH3:80])([CH3:79])[CH3:78])=[O:81])=[CH:20][N:21]=[CH:22][C:23]=3[CH:24]=[CH:25][CH:26]=2)(=[O:16])=[O:15])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 634876Binap, (A+-)-HCID 67242852(S)-3-(tert-Butoxycarbonylamino)-1-(4-bromo-5-isoquinolinesulfonyl)pyrrolidine

Product 1

HCID 67243814(S)-3-(tert-Butoxycarbonylamino)-1-[4-(tert-butoxycarbonylamino)-5-isoquinolinesulfonyl]pyrrolidineYield 32.5%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of Intermediate 1a (137 mg) obtained in Example 1-1, Step A, tris(dibenzylideneacetone)dipalladium(0) (55 mg, Aldrich), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (37 mg, Aldrich), tert-butyl carbamate (70 mg, Aldrich), and cesium carbonate (196 mg, Aldrich) in toluene (5 ml) was stirred at 100° C. for 15 hours. The reaction mixture was cooled to room temperature, and then added with ethyl acetate (5 ml), and the insoluble solids were removed by filtration through Celite. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (n-hexane:ethyl acetate=1:1) to obtain the title compound (48 mg).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customthe insoluble solids were removed by filtration through Celite
  3. customThe solvent was evaporated under reduced pressure
  4. customthe residue was purified by silica gel chromatography (n-hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-554aa971e3714b649e9036c3f4ad7459
Source dataset
uspto-grants-2013_04
Patent number
US08415372B2

Reaction notes

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