Potassium Phosphate, Tribasic → HCID 86698731, compound

HRID 338389Notes

Reaction equation

HRID 338389 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[NH:7][CH:6]=[C:5]2[C:12]([OH:14])=[O:13].CC1(C)COB([C:22]2[CH:29]=[CH:28][C:27]([C:30]3([OH:34])[CH2:33][CH2:32][CH2:31]3)=[CH:26][C:23]=2[C:24]#[N:25])OC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(O)C.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:11][C:10]1[CH:9]=[C:8]2[C:4]([C:5]([C:12]([OH:14])=[O:13])=[CH:6][NH:7]2)=[CH:3][C:2]=1[C:22]1[CH:29]=[CH:28][C:27]([C:30]2([OH:34])[CH2:31][CH2:32][CH2:33]2)=[CH:26][C:23]=1[C:24]#[N:25]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 86698730HCID 86698730, compoundHCID 866987321467062-16-3

Product 1

HCID 86698731HCID 86698731, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
85 °C

Procedure

A suspension of 5-bromo-6-chloro-1H-indole-3-carboxylic acid (100 mg, 0.54 mmol), 2-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-5-(1-hydroxycyclobutyl)benzonitrile (124 mg, 0.435 mmol), 0.5M aqueous potassium phosphate (1.74 mL, 0.87 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (11 mg, 0.014 mmol) in ethanol (4 mL) was sealed in a microwave tube and heated to 85° C. for 45 minutes. The reaction was diluted with water and extracted with ethyl acetate (2×10 mL). The reaction mixture was filtered through celite and the phases were separated. The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo and the residue was purified by reverse phase chromatography to give the title compound. MS (ES−) 365.1 (M−H)−. Retention time: 1.60 min. Column: Waters Atlantis dC18 4.6×50 mm, 5 μm. Modifier: TFA 0.05%. Gradient: 95% H2O/5% MeCN linear to 5% H2O/95% MeCN over 4.0 min, HOLD at 5% H2O/95% MeCN to 5.0 min. Flow: 2.0 mL/min.

Workup

  1. customwas sealed in a microwave tube
  2. extractionextracted with ethyl acetate (2×10 mL)
  3. filtrationThe reaction mixture was filtered through celite
  4. customthe phases were separated
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customthe residue was purified by reverse phase chromatography

Sources & evidence

ORD record
ord-4831a3d17b2043aa95f6501625102faf
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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