Dichloromethane → HCID 86642420, compound

HRID 1625463Notes

Reaction equation

HRID 1625463 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[N:6]=[C:5]2[NH:19][C:20]([C:22]1[C:23](=[O:37])[N:24]([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([F:35])=[C:31]([F:36])[CH:30]=2)[CH:25]=[CH:26][CH:27]=1)=[O:21].[C:38]1([S:44]([N:47]2[C:51]3=[N:52][CH:53]=[CH:54][CH:55]=[C:50]3[C:49](B3OC(C)(C)C(C)(C)O3)=[CH:48]2)(=[O:46])=[O:45])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=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:38]1([S:44]([N:47]2[C:51]3=[N:52][CH:53]=[CH:54][CH:55]=[C:50]3[C:49]([C:2]3[CH:3]=[C:4]4[C:8](=[CH:9][CH:10]=3)[N:7]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:17])([CH3:18])[CH3:16])[N:6]=[C:5]4[NH:19][C:20]([C:22]3[C:23](=[O:37])[N:24]([CH2:28][C:29]4[CH:34]=[CH:33][C:32]([F:35])=[C:31]([F:36])[CH:30]=4)[CH:25]=[CH:26][CH:27]=3)=[O:21])=[CH:48]2)(=[O:46])=[O:45])[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=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 86642421HCID 86642421, compound

Product 1

HCID 86642420HCID 86642420, compoundYield 41.2%

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 [5-bromo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazol-3-yl]-amide (0.123 g, 0.209 mmol;) and 1-Benzenesulfonyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (88 mg, 0.23 mmol;) and [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (21 mg, 0.025 mmol; Strem;) in 1,4-Dioxane (2.69 mL, 34.4 mmol; Acros;). To this was added 2.0 M of Sodium carbonate in water (0.67 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 2.41 with the correct mass 767.28. 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 66 mg of pure product. ES (+) MS m/e=767.28

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
  7. customto give the crude product
  8. customThe crude was then purified by combiflash

Sources & evidence

ORD record
ord-e964225e7b794f08b6f73c37f1ea7b5f
Source dataset
uspto-grants-2014_07
Patent number
US08778977B2

Reaction notes

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