Citric Acid → HCID 58306940, compound

HRID 1909909Notes

Reaction equation

HRID 1909909 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][C:16]=3[C:18]([NH:20][C@H:21]([C:23]3[CH:31]=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[CH:25][CH:24]=3)[CH3:22])=[O:19])[CH:11]=[CH:10]2)=[CH:4][CH:3]=1.[C:32]1(B(O)O)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(C2C=CC=CC=2)C=CC=CC=1P(C1CCCCC1)C1CCCCC1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[Pd](Cl)Cl.O.O1CCOCC1>[C:32]1([C:2]2[N:7]=[CH:6][C:5]([CH2:8][N:9]3[C:17]4[C:12](=[CH:13][CH:14]=[CH:15][C:16]=4[C:18]([NH:20][C@H:21]([C:23]4[CH:24]=[CH:25][C:26]([C:27]([OH:29])=[O:28])=[CH:30][CH:31]=4)[CH3:22])=[O:19])[CH:11]=[CH:10]3)=[CH:4][CH:3]=2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

9

Reactant 5

HCID 311Citric AcidHCID 62657Potassium Phosphate, TribasicHCID 66827Phenylboronic AcidHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 58307045HCID 58307045, compound

Product 1

HCID 58306940HCID 58306940, compoundYield 40.1%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 4-{(1S)-1-[({1-[(6-chloropyridin-3-yl)methyl]-1H-indol-7-yl}carbonyl)amino]ethyl}benzoic acid (0.15 g), phenylboronic acid (84 mg), tripotassium phosphate (0.22 g), palladium (II) chloride (9.2 mg), and biphenyl-2-yl(dicyclohexyl) phosphine (36 mg) were added dioxane (6.0 mL), water (1.5 mL), followed by stirring at 100° C. for 1 hour. The reaction mixture was adjusted to pH 3 by adding a 10% aqueous citric acid solution. The mixed liquid was filtered through Celite, and the filtrate was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/THF=2/1-1/1) to obtain 4-{(1S)-1-[({1-[(6-phenylpyridin-3-yl)methyl]-1H-indol-7-yl}carbonyl)amino]ethyl}benzoic acid (66 mg).

Workup

  1. filtrationThe mixed liquid was filtered through Celite
  2. extractionthe filtrate was extracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (hexane/THF=2/1-1/1)

Sources & evidence

ORD record
ord-89854cf50c8f431d8f0251dfcf88578d
Source dataset
uspto-grants-2013_12
Patent number
US08598355B2

Reaction notes

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