Dichloromethane → (R)-3-[5-(1-Benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-thiophen-2-yl]-3-{[1-(3,4-difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-propionic acid methyl ester

HRID 1625467Notes

Reaction equation

HRID 1625467 reaction equation
[CH3:1][O:2][C:3](=[O:31])[CH2:4][C@H:5]([C:25]1[S:26][C:27](Br)=[CH:28][CH:29]=1)[NH:6][C:7]([C:9]1[C:10](=[O:24])[N:11]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([F:22])=[C:18]([F:23])[CH:17]=2)[CH:12]=[CH:13][CH:14]=1)=[O:8].[C:32]1([S:38]([N:41]2[C:45]3=[N:46][CH:47]=[CH:48][CH:49]=[C:44]3[C:43](B3OC(C)(C)C(C)(C)O3)=[CH:42]2)(=[O:40])=[O:39])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=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]>[CH3:1][O:2][C:3](=[O:31])[CH2:4][C@H:5]([C:25]1[S:26][C:27]([C:43]2[C:44]3[C:45](=[N:46][CH:47]=[CH:48][CH:49]=3)[N:41]([S:38]([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)(=[O:40])=[O:39])[CH:42]=2)=[CH:28][CH:29]=1)[NH:6][C:7]([C:9]1[C:10](=[O:24])[N:11]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([F:22])=[C:18]([F:23])[CH:17]=2)[CH:12]=[CH:13][CH:14]=1)=[O:8]

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 68606715(R)-3-(5-Bromo-thiophen-2-yl)-3-{[1-(3,4-difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-propionic acid methyl ester

Product 1

HCID 68609564(R)-3-[5-(1-Benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-thiophen-2-yl]-3-{[1-(3,4-difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-propionic acid methyl ester

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 (R)-3-(5-Bromo-thiophen-2-yl)-3-{[1-(3,4-difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-propionic acid methyl ester (0.080 g, 0.16 mmol;), 1-Benzenesulfonyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (50 mg, 0.1 mmol;) and [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (17 mg, 0.021 mmol; Strem;) in 1,4-Dioxane (2.21 mL, 28.4 mmol; Acros;). To this was added 2.0 M of Sodium carbonate in water (0.55 mL). The reaction was purged with Argon 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 1.97 with the correct mass 689.16. 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 dissolved in dichloromethane and the purified by combiflash using a 0-100 percent hexanes/ea gradient to give the pure product. ES (+) MS m/e=689.16

Workup

  1. customThe reaction was purged with Argon
  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-2a0bb31a05454039bd2f14a3b669203b
Source dataset
uspto-grants-2014_07
Patent number
US08778977B2

Reaction notes

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