Potassium Phosphate, Tribasic → (r/s)-3-(Tert-butoxycarbonylamino)-1-(4-cyclopropyl-5-isoquinolinesulfonyl)-pyrrolidine

HRID 1436028Notes

Reaction equation

HRID 1436028 reaction equation
[C:1]([O:5][C:6]([NH:8][CH: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][CH: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]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 11710396Tricyclohexylphosphonium TetrafluoroborateHCID 67242856(r/s)-3-(Tert-butoxycarbonylamino)-1-(4-bromo-5-isoquinolinesulfonyl)pyrrolidine

Product 1

HCID 67243197(r/s)-3-(Tert-butoxycarbonylamino)-1-(4-cyclopropyl-5-isoquinolinesulfonyl)-pyrrolidineYield 29%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
80 °C

Procedure

A suspension of Intermediate 1 (200 mg) obtained in Example 1, Step A, cyclopropylboronic acid (57 mg, Aldrich), anhydrous potassium phosphate (372 mg, Aldrich), and tricyclohexylphosphonium tetrafluoroborate (33 mg, Aldrich) in toluene (2 ml) is added with palladium acetate (10 mg, Wako Pure Chemical Industries), and the mixture is stirred at 80° C. with heating for 14 hours under a nitrogen gas atmosphere. The reaction mixture is cooled to room temperature, and then added with ethyl acetate (5 ml), and the insoluble matters are removed by filtration through Celite. The solvent is evaporated under reduced pressure, and the residue is purified by silica gel chromatography (n-hexane:ethyl acetate=1:1) to obtain the title compound (53 mg (predictive yield)).

Workup

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

Sources & evidence

ORD record
ord-7039711c016d46e698c16c69b7758b34
Source dataset
uspto-grants-2009_11
Patent number
US07618984B2

Reaction notes

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