Sodium Carbonate → N-(3-(2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)acrylamide

HRID 1500832Notes

Reaction equation

HRID 1500832 reaction equation
Br[C:2]1[CH:3]=[C:4]2[CH2:10][C:9](=[O:11])[NH:8][C:5]2=[N:6][CH:7]=1.CC1C2C(=NC=C([C:22]3[CH:23]=[C:24]([NH:28][C:29](=[O:34])[C:30]#[C:31]CC)[CH:25]=[CH:26][CH:27]=3)C=2)NC=1.C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[Li+]>C1(C)C=CC=CC=1.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]>[O:11]=[C:9]1[NH:8][C:5]2=[N:6][CH:7]=[C:2]([C:26]3[CH:25]=[C:24]([NH:28][C:29](=[O:34])[CH:30]=[CH2:31])[CH:23]=[CH:22][CH:27]=3)[CH:3]=[C:4]2[CH2:10]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 155040625-bromo-1H,2H,3H-pyrrolo(2,3-b)pyridin-2-oneHCID 86301781N-(3-(3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)pent-2-ynamide

Product 1

HCID 86300420N-(3-(2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)acrylamide

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 86587398Ethanol toluene waterSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 5-bromo-1H-pyrrolo[2,3-b]pyridin-2(3H)-one 149 (100 mg, 0.4673 mmol) and (3-acrylamidophenyl)boronic acid 64 (98.55 mg, 0.514 mmol) in toluene/ethanol/water was added sodium carbonate (198 mg, 1.8692 mmol). Lithium chloride (59.3 mg, 1.40 mmol) was added to the reaction. The reaction was degassed and purged nitrogen for 10 min. Pd(dppf)Cl2 (19.03 mg, 0.0233 mmol) was added to the reaction. The reaction was degassed and purged with nitrogen for another 10 min. The reaction was heated to 90° C. under sealed condition for overnight. The reaction mixture was allowed to cool to room temperature, diluted with chloroform. The organic layer was filtered through celite plug and concentrated to get the crude. The crude was purified through flash chromatography by using 100-200 mesh silica gel. The compound was eluted in ethyl acetate in hexane as half white solid N-(3-(2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)acrylamide 150. MS-ES+338.9, 1H NMR (400 MHz, DMSO): 11.09 (s, 1H), 10.24 (s, 1H), 8.30 (s, 1H), 7.97 (s, 1H), 7.61 (d, 1H), 7.35 (m, 2H), 6.44 (m, 1H), 6.25 (d, 1H), 5.76 (d, 1H), 3.63 (s, 2H).

Workup

  1. customThe reaction was degassed
  2. custompurged nitrogen for 10 min
  3. customThe reaction was degassed
  4. custompurged with nitrogen for another 10 min
  5. customunder sealed condition for overnight
  6. temperatureto cool to room temperature
  7. additiondiluted with chloroform
  8. filtrationThe organic layer was filtered through celite plug
  9. concentrationconcentrated
  10. customto get the crude
  11. customThe crude was purified through flash chromatography
  12. washThe compound was eluted in ethyl acetate in hexane as half white solid N-(3-(2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)acrylamide 150

Sources & evidence

ORD record
ord-6fc9638f69a34cf89069914ab14a4953
Source dataset
uspto-grants-2015_12
Patent number
US09206188B2

Reaction notes

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