Trifluoroacetic acid → HCID 59854563, compound

HRID 2375941Notes

Reaction equation

HRID 2375941 reaction equation
C1(S([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([Br:20])[C:18](Cl)=[C:13]3[CH:12]=[C:11]2[I:21])(=O)=O)C=CC=CC=1.BrC1C(Cl)=C2C=C(I)N(S(C3C=CC=CC=3I)(=O)=O)C2=[N:27]C=1.FC(F)(F)C(O)=O.[NH:51]1[C:59]2[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=2)[CH:53]=[N:52]1>C(O)C(F)(F)F.CO.C(=O)(O)[O-].[Na+]>[Br:20][C:17]1[C:18]([NH:27][C:56]2[CH:55]=[C:54]3[C:59](=[CH:58][CH:57]=2)[NH:51][N:52]=[CH:53]3)=[C:13]2[CH:12]=[C:11]([I:21])[NH:10][C:14]2=[N:15][CH:16]=1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 92211H-Indazole2×HCID 59854535HCID 59854535, compoundHCID 59854553HCID 59854553, compound

Product 1

HCID 59854563HCID 59854563, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 64092,2,2-TrifluoroethanolSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
120 °C

Procedure

To a slurry of a mixture of 1-benzenesulfonyl-5-bromo-4-chloro-2-iodo-1H-pyrrolo[2,3-b]pyridine and 5-bromo-4-chloro-2-iodo-1-(2-iodobenzenesulfonyl)-1H-pyrrolo[2,3-b]pyridine (560 mg, 1.0 mmol) in trifluoroethanol (6 mL) was added trifluoroacetic acid (0.041 mL, 0.52 mmol) and indazole (266 mg, 2.0 mmol), and the reaction was heated in a sealed tube at 120° C. for 4 d. Additional indazole (67 mg, 0.5 mmol) was added twice to the reaction on the second and third days. The reaction was cooled to RT, diluted with methanol (20 mL), saturated sodium bicarbonate solution was added (1 mL) and evaporated to dryness under reduced pressure. The residue obtained was triturated with methanol:DCM (1:1) mixture and filtered. The filtrate was evaporated and the crude obtained was purified by chromatography on silica gel [Jones Flashmaster, 70 g/150 mL cartridge, eluting with DCM:Methanol 100:0→96:4], yielding the product, which was triturated with 4:1 methanol:DCM mixture and filtered. The precipitate obtained was dried under vacuum to afford the title compound as an off-white solid. The low polar fractions from the column were combined, evaporated and the residue was stirred with 3N NaOH in methanol (2 mL) for 30 min and quenched with saturated ammonium chloride solution (2 mL). Water (10 mL) was added and filtered to afford additional title compound. MS (ES+): m/z 453.63 (100) [MH+]; HPLC: tR=2.58 min (ZQ2000, polar—5 min).

Workup

  1. temperatureThe reaction was cooled to RT
  2. additionwas added (1 mL)
  3. customevaporated to dryness under reduced pressure
  4. customThe residue obtained
  5. customwas triturated with methanol:DCM (1:1) mixture
  6. filtrationfiltered
  7. customThe filtrate was evaporated
  8. customthe crude obtained
  9. customwas purified by chromatography on silica gel [Jones Flashmaster, 70 g/150 mL cartridge, eluting with DCM:Methanol 100:0→96:4]
  10. customyielding the product, which
  11. customwas triturated with 4:1 methanol
  12. filtrationDCM mixture and filtered
  13. customThe precipitate obtained
  14. customwas dried under vacuum

Sources & evidence

ORD record
ord-82d642c769f84621adb54d0307621f3d
Source dataset
uspto-grants-2008_12
Patent number
US07465726B2

Reaction notes

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