Dichloromethane → HCID 59540521, compound

HRID 1677424Notes

Reaction equation

HRID 1677424 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.[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22](B2OC(C)(C)C(C)(C)O2)=[CH:21][C:20]=1[N:34]1[CH2:38][CH2:37][CH2:36][CH2:35]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>[CH3:17][O:18][C:19]1[CH:24]=[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][C:20]=1[N:34]1[CH2:38][CH2:37][CH2:36][CH2:35]1

Participants

8

Reactant 4

HCID 6344Dichloromethane2×HCID 11430Potassium CarbonateHCID 578292181-(2-Bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethylpropan-1-oneHCID 59541023HCID 59541023, compound

Product 1

HCID 59540521HCID 59540521, compoundYield 29.4%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 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 (50 mg, 0.18 mmol), 1-[2-methoxy-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-pyrrolidine (60 mg, 0.2 mmol), potassium carbonate (63 mg, 0.46 mmol), Pd(dppf)Cl2.CH2Cl2 (11 mg, 0.013 mmol), 1.4 mL dioxane and 0.3 mL water was stirred at 150° C. in a microwave for 30 min. The resulting mixture was treated with additional Pd(dppf)Cl2.CH2Cl2 (2 mg, 0.002 mmol), stirred at 160° C. in a microwave for 10 min, and partitioned between ethyl acetate and water. The combined organic layers were dried over Na2SO4 and concentrated to give a dark brown residue. The crude product was purified by preparative thin layer chromatography using 140:9.5:0.5 CH2Cl2:MeOH:conc NH4OH as eluant. The resultant brown solid was washed with CH2Cl2 and ethyl ether to provide 20 mg (29%) of 1-[2-(4-methoxy-3-pyrrolidin-1-yl-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one as a yellow solid. MP 211-213° C., M+H 379.

Workup

  1. custompartitioned between ethyl acetate and water
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. concentrationconcentrated
  4. customto give a dark brown residue
  5. customThe crude product was purified by preparative thin layer chromatography
  6. washThe resultant brown solid was washed with CH2Cl2 and ethyl ether

Sources & evidence

ORD record
ord-cf306b5bbb9c4f2aa9817965638af742
Source dataset
uspto-grants-2011_08
Patent number
US08008298B2

Reaction notes

Loading…