Toluene → 5-{4-[2-(azetidin-1-yl)-2-oxoethyl]phenyl}-6-chloro-1H-indole-3-carbaldehyde

HRID 338248

Reaction equation

HRID 338248 reaction equation
[N:1]1([C:5](=[O:21])[CH2:6][C:7]2[CH:12]=[CH:11][C:10](B3OCC(C)(C)CO3)=[CH:9][CH:8]=2)[CH2:4][CH2:3][CH2:2]1.Br[C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][C:31]=1[Cl:32])[NH:28][CH:27]=[C:26]2[CH:33]=[O:34].C([O-])([O-])=O.[K+].[K+].C1(C)C=CC=CC=1>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].CCO>[N:1]1([C:5](=[O:21])[CH2:6][C:7]2[CH:8]=[CH:9][C:10]([C:23]3[CH:24]=[C:25]4[C:29](=[CH:30][C:31]=3[Cl:32])[NH:28][CH:27]=[C:26]4[CH:33]=[O:34])=[CH:11][CH:12]=2)[CH2:2][CH2:3][CH2:4]1

Participants

7

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 866985665-bromo-6-chloro-1H-indole-3-carbaldehydeHCID 866985921-(Azetidin-1-yl)-2-(4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl)ethanone

Product 1

HCID 866985935-{4-[2-(azetidin-1-yl)-2-oxoethyl]phenyl}-6-chloro-1H-indole-3-carbaldehydeYield 42%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

To a degassed mixture of 1-(azetidin-1-yl)-2-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl]ethanone (0.78 g, 2.7 mmol), 5-bromo-6-chloro-1H-indole-3-carbaldehyde (700 mg, 2.7 mmol) and 2M aqueous K2CO3 (5.4 mL, 10.8 mmol) in a solvent mixture of toluene and EtOH (v/v=3/1, 14 mL) was added [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (197.6 mg, 0.27 mmol). The reaction mixture was stirred under microwave irradiation at 120° C. for 30 min. After cooling to room temperature, the reaction mixture was partitioned between water and EtOAc (50 mL/50 mL). The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash column (first EtOAc in Petroleum 25%, then MeOH in DCM 10%) to give 5-{4-[2-(azetidin-1-yl)-2-oxoethyl]phenyl}-6-chloro-1H-indole-3-carbaldehyde (0.4 g, 42%) as a brown solid.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe reaction mixture was partitioned between water and EtOAc (50 mL/50 mL)
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column (first EtOAc in Petroleum 25%

Sources & evidence

ORD record
ord-dba872cbc83d43a692d6c1a742bc1fb3
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Linked notes

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