Pyrrolidine → HCID 24957616, compound

HRID 244430Notes

Reaction equation

HRID 244430 reaction equation
[CH2:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10](Br)[CH:11]=2)[C:6]([C:14]([C:20]2[CH:21]=[C:22]3[C:26](=[CH:27][CH:28]=2)[N:25]([C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=2)[N:24]=[CH:23]3)([OH:19])[C:15]([F:18])([F:17])[F:16])=[CH:5]1)[CH:2]=[CH2:3].[NH:36]1[CH2:40][CH2:39][CH2:38][CH2:37]1.CC(C)([O-])C.[Na+]>[Pd].O1CCOCC1>[CH2:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([N:36]3[CH2:40][CH2:39][CH2:38][CH2:37]3)[CH:11]=2)[C:6]([C:14]([C:20]2[CH:21]=[C:22]3[C:26](=[CH:27][CH:28]=2)[N:25]([C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=2)[N:24]=[CH:23]3)([OH:19])[C:15]([F:18])([F:17])[F:16])=[CH:5]1)[CH:2]=[CH2:3]

Participants

6

Reactant 3

HCID 31268PyrrolidineHCID 23676156Sodium t-butoxideHCID 24957617HCID 24957617, compound

Product 1

HCID 24957616HCID 24957616, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 0.1 g (0.18 mmol) of 1-(1-allyl-6-bromo-1H-indol-3-yl)-2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanol, 28.0 mg (0.4 mmol) of pyrrolidine, 5.0 mg of Pd catalyst (prepared according to a procedure described in Org. Lett. 2003 14 2413-2415), and 35.0 mg (0.36 mmol) of sodium tert-butoxide in 10 mL of dioxane was warmed at 90° C. After 2 hours, the mixture was cooled to room temperature, filtered through CELITE® filter aid, diluted with water, and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography using ethyl acetate in hexanes (30-80% gradient). The major fractions were combined and concentrated in vacuo to afford 21.0 mg 21.4%) of the title compound. MS m/z 534.5 (MH+).

Workup

  1. customprepared
  2. filtrationfiltered through CELITE®
  3. filtrationfilter aid
  4. additiondiluted with water
  5. extractionextracted with ethyl acetate
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6e8fbe0e54fb4e00afcb09911c305bee
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Reaction notes

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