Acetonitrile → HCID 178489414, compound

HRID 2388944Notes

Reaction equation

HRID 2388944 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15](B3OC(C)(C)C(C)(C)O3)[CH:16]=2)[N:11](COCC[Si](C)(C)C)C=1.C[O:36][C:37]([C:39]1[S:43][C:42](Br)=[N:41][CH:40]=1)=[O:38].C(#[N:47])C.C([O-])([O-])=O.[Na+].[Na+]>CCOCC>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:42]3[S:43][C:39]([C:37]([OH:36])=[O:38])=[CH:40][N:41]=3)[CH:16]=2)[NH:11][N:47]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 2773502Methyl 2-bromothiazole-5-carboxylateHCID 598248843-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 178489414HCID 178489414, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

Into a 20 mL Personal Chemistry microwave reaction vial were added 3-(2-Methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine (0.4992 g, 1.038 mmol), 2-Bromo-thiazole-5-carboxylic acid methyl ester (0.2592 g, 1.167 mmol), 1,1′-bis(diphenylphosphino)ferrocenepalladium(II)-dichloride dichloromethane adduct (95.4 mg, 0.117 mmol), acetonitrile (5 mL) and 2M aqueous Na2CO3 (5 mL). The vial was sealed, purged with N2, and irradiated in a Personal Chemistry Optimizer at 130° C. for 30 min. The reaction mixture was diluted with EtOAc and acidified with acetic acid to pH 5. The layers were separated, and the aqueous phase was extracted 5× with EtOAc. The combined organic phase was treated with brine, dried (Na2SO4), filtered and concentrated. The crude product was dissolved in 10 mL of a solution consisting of 1 part HClO4 (70%, ACS) and 20 parts glacial acetic acid, and the solution was stirred at rt for 4 h. The reaction mixture was concentrated under vacuum, and neutralized to pH 7 with saturated NaHCO3 followed by solid NaHCO3. The quenched reaction mixture was partitioned between EtOAc and water, the layers were separated, and the aqueous phase was extracted 2× with EtOAc. The aqueous phase was then acidified to pH 4 with acetic acid and extracted 5× with EtOAc. The combined organic extracts was treated with brine, dried (Na2SO4), filtered and concentrated. Trituration with Et2O afforded the title compound as a greenish-brown powder (0.296 g, 81% yield). 1H-NMR (500 MHz, d6-DMSO) δ 13.73 (br. s, 1H), 9.16 (s, 1H), 8.71 (s, 1H), 8.40 (s, 1H), 7.68 (d, J=8.0 Hz, 1H), 7.48 (t, J=8.0 Hz, 2H), 7.24 (d, J=8.0 Hz, 1H), 7.10 (t, J=7.5 Hz 1H), 3.87 (s, 3H); MS: m/z 353.1 [MH+].

Workup

  1. customInto a 20 mL Personal Chemistry microwave reaction
  2. customThe vial was sealed
  3. custompurged with N2
  4. customirradiated in a Personal Chemistry Optimizer at 130° C. for 30 min
  5. additionThe reaction mixture was diluted with EtOAc
  6. customThe layers were separated
  7. extractionthe aqueous phase was extracted 5× with EtOAc
  8. additionThe combined organic phase was treated with brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. dissolutionThe crude product was dissolved in 10 mL of a solution
  13. concentrationThe reaction mixture was concentrated under vacuum
  14. customThe quenched reaction mixture
  15. customwas partitioned between EtOAc and water
  16. customthe layers were separated
  17. extractionthe aqueous phase was extracted 2× with EtOAc
  18. extractionextracted 5× with EtOAc
  19. additionThe combined organic extracts was treated with brine
  20. dry with materialdried (Na2SO4)
  21. filtrationfiltered
  22. concentrationconcentrated

Sources & evidence

ORD record
ord-f409532a6f034a108d0c539071bbd9f9
Source dataset
uspto-grants-2012_09
Patent number
US08268994B2

Reaction notes

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