Dichloromethane → 1-[2-(2-chloro-pyridin-4-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one

HRID 547465Notes

Reaction equation

HRID 547465 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11](=[O:16])[C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[Cl:17][C:18]1[CH:23]=[C:22](B(O)O)[CH:21]=[CH:20][N:19]=1.C(=O)([O-])[O-].[K+].[K+].C(Cl)Cl>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.O1CCOCC1>[Cl:17][C:18]1[CH:23]=[C:22]([C:2]2[N:3]=[C:4]3[C:10]([C:11](=[O:16])[C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:9][NH:8][C:5]3=[N:6][CH:7]=2)[CH:21]=[CH:20][N:19]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 51515952-Chloropyridine-4-boronic acidHCID 578292181-(2-Bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethylpropan-1-one

Product 1

HCID 578296311-[2-(2-chloro-pyridin-4-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-oneYield 32.2%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 1-(2-bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethyl-propan-1-one (0.430 g, 1.53 mmol), 2-chloropyridine-4-boronic acid (0.362 g, 2.30 mmol), potassium carbonate (0.782 g, 5.66 mmol), Pd(dppf)Cl2.CH2Cl2 (0.098 g, 0.12 mmol), 10 mL dioxane and 2.5 mL water was stirred at 160° C. in a microwave for 30 min. The resulting red mixture was partitioned between 80 mL of ethyl acetate and 150 mL of water. The aqueous layer was extracted with two 80 mL portions of ethyl acetate. The combined organic layers were dried over MgSO4, filtered and concentrated to a residue. Silica gel chromatography (0->100% EtOAc/hexanes) afforded 0.155 g (32%) of 1-[2-(2-chloro-pyridin-4-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one as a red solid.

Workup

  1. customThe resulting red mixture was partitioned between 80 mL of ethyl acetate and 150 mL of water
  2. extractionThe aqueous layer was extracted with two 80 mL portions of ethyl acetate
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated to a residue

Sources & evidence

ORD record
ord-feb5d30db265411ca606a4ad99d353a5
Source dataset
uspto-grants-2011_05
Patent number
US07939531B2

Reaction notes

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