Ethyl 5-bromopyridine-3-carboxylate → 5-[3-(2-Methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]nicotinic acid ethyl ester

HRID 901362Notes

Reaction equation

HRID 901362 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]([S:27]([C:30]2[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=2)(=[O:29])=[O:28])[CH:10]=1.[CH2:37]([O:39][C:40](=[O:48])[C:41]1[CH:46]=[C:45](Br)[CH:44]=[N:43][CH:42]=1)[CH3:38].C([O-])(O)=O.[Na+]>C(#N)C>[CH2:37]([O:39][C:40](=[O:48])[C:41]1[CH:46]=[C:45]([C:15]2[CH:16]=[C:17]3[C:9]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[O:2][CH3:1])=[CH:10][N:11]([S:27]([C:30]4[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=4)(=[O:28])=[O:29])[C:12]3=[N:13][CH:14]=2)[CH:44]=[N:43][CH:42]=1)[CH3:38]

Participants

5

Reactant 3

HCID 140785Ethyl 5-bromopyridine-3-carboxylateHCID 516892Sodium BicarbonateHCID 160390673-(2-Methoxyphenyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 596999005-[3-(2-Methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]nicotinic acid ethyl esterYield 69%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

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-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine (0.995 g, 2.18 mmol), 5-Bromo-nicotinic acid ethyl ester (0.645 g, 2.33 mmol), 1,1′-bis(diphenylphosphino)ferrocenepalladium(II)-dichloride dichloromethane adduct (95.5 mg, 0.117 mmol), acetonitrile (10 mL) and saturated aqueous NaHCO3 (10 mL). The vial was sealed, purged with N2, and irradiated in a Personal Chemistry Optimizer at 90° C. for 15 min. The layers were separated, and the aqueous phase was extracted 3× with EtOAc. The combined organic phase was treated with brine, dried (Na2SO4), filtered and concentrated. Purification by flash silica gel chromatography using a gradient of ethyl acetate and hexanes afforded 5-[3-(2-Methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-nicotinic acid ethyl ester as a white powder (0.794 g, 69%). MS: m/z 528.1 [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 90° C. for 15 min
  5. customThe layers were separated
  6. extractionthe aqueous phase was extracted 3× with EtOAc
  7. additionThe combined organic phase was treated with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification by flash silica gel chromatography

Sources & evidence

ORD record
ord-17c1fa453bd246da93d5bf0b0223ed49
Source dataset
uspto-grants-2008_04
Patent number
US07361763B2

Reaction notes

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