3-Bromopyridine → ethyl 3-((6-chloro-7-fluoro-1-(pyridin-3-yl)-1H-indol-3-yl)thio)-2-fluorobenzoate

HRID 522792Notes

Reaction equation

HRID 522792 reaction equation
[Cl:1][C:2]1[C:10]([F:11])=[C:9]2[C:5]([C:6]([S:12][C:13]3[C:14]([F:24])=[C:15]([CH:21]=[CH:22][CH:23]=3)[C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.Br[C:26]1[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=1.N[C@@H]1CCCC[C@H]1N.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:10]([F:11])=[C:9]2[C:5]([C:6]([S:12][C:13]3[C:14]([F:24])=[C:15]([CH:21]=[CH:22][CH:23]=3)[C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:7][N:8]2[C:26]2[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 122863-BromopyridineHCID 438061,2-Diaminocyclohexane, trans-HCID 62657Potassium Phosphate, TribasicHCID 117979430ethyl 3-((6-chloro-7-fluoro-1H-indol-3-yl)thio)-2-fluorobenzoate

Product 1

HCID 118104184ethyl 3-((6-chloro-7-fluoro-1-(pyridin-3-yl)-1H-indol-3-yl)thio)-2-fluorobenzoateYield 54.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
140 °C

Procedure

To a stirred solution of compound 2 (200 mg, 0.54 mmol) in toluene (5 mL) were added 3-bromopyridine (131 mg, 0.81 mmol), trans-1,2-diaminocyclohexane (24.8 mg, 0.21 mmol), K3PO4 (288 mg, 1.35 mmol), Cu(I)I (10.3 mg, 0.05 mmol) at RT under inert atmosphere. The mixture was purged with argon for 15 min and heated to 140° C. in a sealed tube for 16 h. The reaction mixture was cooled to RT, added n-hexane (6 mL), stirred for 5 minutes and then filtered. The filtrate was diluted with water (20 mL) and extracted with EtOAc (2×50 mL). The combined organic extracts were washed with water and brine solution, dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. The crude was purified (silica gel; 10-12% EtOAc/Hexanes) to afford compound 3 (130 mg, 54%) as an off-white solid.

Workup

  1. customThe mixture was purged with argon for 15 min
  2. temperatureThe reaction mixture was cooled to RT
  3. additionadded n-hexane (6 mL)
  4. filtrationfiltered
  5. additionThe filtrate was diluted with water (20 mL)
  6. extractionextracted with EtOAc (2×50 mL)
  7. washThe combined organic extracts were washed with water and brine solution
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto obtain the crude
  12. customThe crude was purified (silica gel; 10-12% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-b1b6f4dbd3ae4236a79757cd38b060f1
Source dataset
uspto-grants-2016_05
Patent number
US09334261B2

Reaction notes

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