Dichloromethane → 2,2-dimethyl-1-[2-(3,4,5-trimethoxy-phenyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-pent-4-en-1-one

HRID 1677514Notes

Reaction equation

HRID 1677514 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11](=[O:18])[C:12]([CH3:17])([CH3:16])[CH2:13][CH:14]=[CH2:15])=[CH:9][N:8]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:5]2=[N:6][CH:7]=1.[CH3:27][O:28][C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[C:33]([O:37][CH3:38])[C:34]=1[O:35][CH3:36].C(=O)([O-])[O-].[K+].[K+].C(Cl)Cl>O1CCOCC1.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]>[CH3:16][C:12]([CH3:17])([CH2:13][CH:14]=[CH2:15])[C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([C:31]3[CH:32]=[C:33]([O:37][CH3:38])[C:34]([O:35][CH3:36])=[C:29]([O:28][CH3:27])[CH:30]=3)[N:3]=2)[N:8]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[CH:9]=1)=[O:18]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 27343903,4,5-Trimethoxybenzeneboronic acidHCID 595406911-[2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-pent-4-en-1-one

Product 1

HCID 595408992,2-dimethyl-1-[2-(3,4,5-trimethoxy-phenyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-pent-4-en-1-oneYield 72.1%

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 impure 1-[2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-pent-4-en-1-one (0.900 g, “2.05 mmol), 3,4,5-trimethoxyphenyl boronic acid (0.479 g, 2.26 mmol), potassium carbonate (0.850 g, 6.15 mmol) and Pd(dppf)Cl2.CH2Cl2 (0.171 g, 0.21 mmol) in 15 mL of 1,4-dioxane and 4 mL of water was stirred at 120° C. in a microwave for 1 h. The resulting mixture was partitioned between 300 mL of ethyl acetate and 200 mL of water. The organic layer was dried over MgSO4, filtered and concentrated to a residue. Column chromatography (0→35% EtOAc/hexanes) afforded 0.777 g (29% for three steps from 2-bromo-5H-pyrrolo[2,3-b]pyrazine) of 2,2-dimethyl-1-[2-(3,4,5-trimethoxy-phenyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-pent-4-en-1-one.

Workup

  1. customThe resulting mixture was partitioned between 300 mL of ethyl acetate and 200 mL of water
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated to a residue

Sources & evidence

ORD record
ord-5ed26acf7e4040aeb892c1fd3ff964bf
Source dataset
uspto-grants-2011_08
Patent number
US08008298B2

Reaction notes

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