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Potassium Phosphate, Tribasic → (S)-3-(tert-Butoxycarbonylamino)-1-(4-cyclopropyl-5-isoquinolinesulfonyl)pyrrolidine

HRID 1962432
Notes
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Reaction equation

HRID 1962432 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].[CH:28]1(B(O)O)[CH2:30][CH2:29]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].F[B-](F)(F)F.C1([PH+](C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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]([CH:28]4[CH2:30][CH2:29]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]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 11710396Tricyclohexylphosphonium TetrafluoroborateHCID 67242852(S)-3-(tert-Butoxycarbonylamino)-1-(4-bromo-5-isoquinolinesulfonyl)pyrrolidine

Product 1

HCID 67243196(S)-3-(tert-Butoxycarbonylamino)-1-(4-cyclopropyl-5-isoquinolinesulfonyl)pyrrolidine
Yield 29%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of Intermediate 1a (200 mg) obtained in Example 1-1, Step A, cyclopropylboronic acid (57 mg, Aldrich), anhydrous potassium phosphate (372 mg, Aldrich), and tricyclohexylphosphonium tetrafluoroborate (33 mg, Aldrich) in toluene (2 ml) was added with palladium acetate (10 mg, Wako Pure Chemical Industries), and the mixture was stirred at 80° C. with heating for 14 hours under a nitrogen gas atmosphere. 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 (53 mg).

Workup

  1. temperaturewith heating for 14 hours under a nitrogen gas atmosphere
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customthe insoluble solids were removed by filtration through Celite
  4. customThe solvent was evaporated under reduced pressure
  5. customthe residue was purified by silica gel chromatography (n-hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-d67768e3bd00415a97a2653785651add
Source dataset
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08415372B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes