Dichloromethane → 1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carboxylic acid [4-(1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-thiophen-2-ylmethyl]-amide

HRID 1625481Notes

Reaction equation

HRID 1625481 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:7][NH:8][C:9]([C:11]2[C:12](=[O:26])[N:13]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[C:20]([F:25])[CH:19]=3)[CH:14]=[CH:15][CH:16]=2)=[O:10])[S:5][CH:6]=1.[C:27]1([S:33]([N:36]2[C:40]3=[N:41][CH:42]=[CH:43][CH:44]=[C:39]3[C:38](B3OC(C)(C)C(C)(C)O3)=[CH:37]2)(=[O:35])=[O:34])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.ClCCl.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>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]>[C:27]1([S:33]([N:36]2[C:40]3=[N:41][CH:42]=[CH:43][CH:44]=[C:39]3[C:38]([C:2]3[CH:3]=[C:4]([CH2:7][NH:8][C:9]([C:11]4[C:12](=[O:26])[N:13]([CH2:17][C:18]5[CH:23]=[CH:22][C:21]([F:24])=[C:20]([F:25])[CH:19]=5)[CH:14]=[CH:15][CH:16]=4)=[O:10])[S:5][CH:6]=3)=[CH:37]2)(=[O:35])=[O:34])[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

8

Reactant 5

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 455881371-(Phenylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridineHCID 593627111-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carboxylic acid (4-bromo-thiophen-2-ylmethyl)-amide

Product 1

HCID 866424221-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carboxylic acid [4-(1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-thiophen-2-ylmethyl]-amide

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

Into a Vial was dissolved 1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carboxylic acid (4-bromo-thiophen-2-ylmethyl)-amide (0.0953 g, 0.217 mmol;), 1-Benzenesulfonyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (100 mg, 0.3 mmol;) and [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (28 mg, 0.035 mmol; Strem;) in 1,4-Dioxane (3.69 mL, 47.3 mmol; Acros;). To this was added 2.0 M of Sodium carbonate in water (0.92 mL). The reaction was purged with Ar and sealed. The reaction was heated at 100° C. under an atmosphere of Argon for 2 hours. LC-MS showed the formation of product at 1.80 with the correct mass 661.13. The reaction was worked up by dissolving in methylene chloride then washing 1× with citric acid, 1× with saturated bicarbonate and 1× with brine before drying with magnesium sulfate and concentrating to give the crude product. The crude was then purified by combiflash using a 0-100 percent hex/ea gradient to give pure product. ES (+) MS m/e=661.13

Workup

  1. customThe reaction was purged with Ar
  2. customsealed
  3. dissolutionby dissolving in methylene chloride
  4. washthen washing 1× with citric acid, 1× with saturated bicarbonate and 1× with brine
  5. dry with materialbefore drying with magnesium sulfate
  6. concentrationconcentrating

Sources & evidence

ORD record
ord-dc153b7606d3434a8fce81ec36676213
Source dataset
uspto-grants-2014_07
Patent number
US08778977B2

Reaction notes

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