5-bromo-1-(4-fluorophenyl)-1H-indazole → 3-{2,2,2-Trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}pyrrolo[2,3-b]pyridine-1-sulfonic acid dimethylamide

HRID 244398Notes

Reaction equation

HRID 244398 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)[N:6]=[CH:5]2.[Li]CCCC.[CH3:23][N:24]([CH3:43])[S:25]([N:28]1[C:32]2=[N:33][CH:34]=[CH:35][CH:36]=[C:31]2[C:30]([C:37](=[O:42])[C:38]([F:41])([F:40])[F:39])=[CH:29]1)(=[O:27])=[O:26]>C1COCC1.CCCCCC.[Cl-].[NH4+]>[CH3:23][N:24]([CH3:43])[S:25]([N:28]1[C:32]2=[N:33][CH:34]=[CH:35][CH:36]=[C:31]2[C:30]([C:37]([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[N:7]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[N:6]=[CH:5]3)([OH:42])[C:38]([F:39])([F:41])[F:40])=[CH:29]1)(=[O:26])=[O:27]

Participants

7

Reactant 3

HCID 468307945-bromo-1-(4-fluorophenyl)-1H-indazoleHCID 497590101H-Pyrrolo[2,3-B]pyridine-1-sulfonamide, N,N-dimethyl-3-(2,2,2-trifluoroacetyl)-HCID 178418339Butyllithium

Product 1

HCID 249590943-{2,2,2-Trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}pyrrolo[2,3-b]pyridine-1-sulfonic acid dimethylamideYield 29.2%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a chilled (−78° C.) solution of 80 mg (0.27 mmol) of 5-bromo-1-(4-fluorophenyl)-1H-indazole in 1 mL of anhydrous THF was added 110 μL (0.28 mmol) of a solution of 2.5 M n-BuLi in hexane in one portion. This solution was then added to a chilled (−78° C.) solution of 88 mg (0.27 mmol) of 3-(2,2,2-trifluoro-acetyl)pyrrolo[2,3-b]pyridine-1-sulfonic acid dimethylamide in 3 mL of THF. The reaction was monitored by TLC (ethyl acetate-hexanes 4:6). After 30 minutes, the mixture was diluted with 7 mL of saturated aqueous ammonium chloride and extracted with three 10 mL portions of ethyl acetate. The combined organic layers were washed with three 10 mL portions of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was chromatographed on silica gel (prep. plate, 2×1 mm, ethyl acetate-hexanes 30:70). The material from the prep plate was washed from the silica gel with ethyl acetate and concentrated. The residue was triturated with ether-hexanes to afford 42 mg (28%) of the title compound. MS m/z 534.22 (MH+).

Workup

  1. additionThis solution was then added to
  2. extractionextracted with three 10 mL portions of ethyl acetate
  3. washThe combined organic layers were washed with three 10 mL portions of brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was chromatographed on silica gel (prep. plate, 2×1 mm, ethyl acetate-hexanes 30:70)
  8. washThe material from the prep plate was washed from the silica gel with ethyl acetate
  9. concentrationconcentrated
  10. customThe residue was triturated with ether-hexanes

Sources & evidence

ORD record
ord-6fb466a246214a55817c9d92d5e0a44a
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Reaction notes

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