1,2-Dimethoxyethane → (S)-3-(tert-Butoxycarbonylamino)-1-[4-phenyl-5-isoquinolinesulfonyl]pyrrolidine

HRID 1962434Notes

Reaction equation

HRID 1962434 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].[C:28]1(B(O)O)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.COCCOC.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[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]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[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

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 67242852(S)-3-(tert-Butoxycarbonylamino)-1-(4-bromo-5-isoquinolinesulfonyl)pyrrolidine

Product 1

HCID 68587283(S)-3-(tert-Butoxycarbonylamino)-1-[4-phenyl-5-isoquinolinesulfonyl]pyrrolidineYield 69.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

Intermediate 1a (228 mg) obtained in Example 1-1, Step A was added with phenylboronic acid (122 mg, Aldrich), tetrakis(triphenylphosphine)palladium(0) (116 mg), 1,2-dimethoxyethane (5 ml) and 2 N aqueous sodium carbonate (2 ml), and the mixture was refluxed by heating for 5 hours under a nitrogen gas atmosphere. The reaction mixture was cooled to room temperature, then added with water (25 ml), and extracted 3 times with ethyl acetate (20 ml for each time), and the combined organic layer was washed with saturated brine (30 ml), and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (n-hexane:ethyl acetate=2:1) to obtain the title compound (158 mg).

Workup

  1. temperaturethe mixture was refluxed
  2. temperatureby heating for 5 hours under a nitrogen gas atmosphere
  3. extractionextracted 3 times with ethyl acetate (20 ml for each time), and the combined organic layer
  4. washwas washed with saturated brine (30 ml)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was purified by silica gel chromatography (n-hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-1bed80e2e9e447cca334c9c013fdd525
Source dataset
uspto-grants-2013_04
Patent number
US08415372B2

Reaction notes

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