2-Fluoro-4-(tributylstannyl)pyridine → 4-(2-Fluoropyridin-4-yl)-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid potassium salt

HRID 513195Notes

Reaction equation

HRID 513195 reaction equation
Cl[C:2]1[C:7]2[CH:8]=[C:9]([C:25]([O:27]C)=[O:26])[N:10]([CH2:11][CH2:12][O:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=3)[C:6]=2[CH:5]=[CH:4][N:3]=1.[F:29][C:30]1[CH:35]=[C:34]([Sn](CCCC)(CCCC)CCCC)[CH:33]=[CH:32][N:31]=1.O([Si](C)(C)C)[K:50]>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.O1CCOCC1>[K+:50].[F:29][C:30]1[CH:35]=[C:34]([C:2]2[C:7]3[CH:8]=[C:9]([C:25]([O-:27])=[O:26])[N:10]([CH2:11][CH2:12][O:13][C:14]4[CH:15]=[CH:16][C:17]([O:20][C:21]([F:22])([F:24])[F:23])=[CH:18][CH:19]=4)[C:6]=3[CH:5]=[CH:4][N:3]=2)[CH:33]=[CH:32][N:31]=1

Participants

6

Reactant 3

HCID 164270992-Fluoro-4-(tributylstannyl)pyridineHCID 86720572Methyl 4-chloro-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylateHCID 178504318HCID 178504318, compound

Product 1

HCID 901862684-(2-Fluoropyridin-4-yl)-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid potassium salt

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Methyl 4-chloro-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylate (50 mg, 0.121 mmole), 2-fluoro-4-(tributylstannyl)pyridine (61 mg, 0.158 mmole), and bis(tri-t-butylphosphine)palladium(0) (6 mg, 0.012 mmole) were combined in a screw cap vial. To this was added 1,4-dioxane (0.5 mL). N2 was bubbled through the mixture for 10 seconds. The vial was capped then heated to 100° C. After stirring overnight the mixture was cooled to RT. Excess QuadraPure was added and stirring continued at RT. After stirring 6 hr the mixture was filtered washing with EtOAc and concentrated. The residue was taken up in 1 mL THF. To this was added KOTMS (47 mg, 0.366 mmole) at RT. After 3 hr the mixture was concentrated. The residue was taken up in Et2O. The resulting off-white solid (53 mg, 88%) was collected by filtration washing with Et2O and dried in vacuo. 1H NMR (400 MHz, DMSO): δ 8.39 (d, J=5.1 Hz, 1 H); 8.35 (d, J=5.9 Hz, 1 H); 7.95 (d, J=5.1 Hz, 1 H); 7.63 (d, J=6.3 Hz, 2 II); 7.21 (d, J=8.4 Hz, 2 H); 7.04 (s, 1 H); 6.95 (d, J=8.8 Hz, 2 H); 5.12-5.05 (m, 2 H); 4.39-4.33 (m, 2 H).

Workup

  1. customcap vial
  2. customN2 was bubbled through the mixture for 10 seconds
  3. customThe vial was capped
  4. temperaturewas cooled to RT
  5. additionExcess QuadraPure was added
  6. stirringstirring
  7. customcontinued at RT
  8. stirringAfter stirring 6 hr the mixture
  9. filtrationwas filtered
  10. washwashing with EtOAc
  11. concentrationconcentrated
  12. concentrationAfter 3 hr the mixture was concentrated
  13. filtrationThe resulting off-white solid (53 mg, 88%) was collected by filtration
  14. washwashing with Et2O
  15. customdried in vacuo

Sources & evidence

ORD record
ord-27d141f7cbbd46a3ad6c5e1adcc60d8c
Source dataset
uspto-grants-2015_08
Patent number
US09102673B2

Reaction notes

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