Tetrahydrofuran → HCID 15986728, compound

HRID 730085Notes

Reaction equation

HRID 730085 reaction equation
[NH2:1][C:2]1[C:15]2OC3C(=CC=CC=3)[C:7](=[C:16]3[CH2:22][CH:21]4[N:23](C(=O)C(F)(F)F)[CH:18]([CH2:19][CH2:20]4)[CH2:17]3)[C:6]=2[CH:5]=[CH:4][CH:3]=1.Br[C:31]1[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=1.C[C:38]([CH3:41])([O-:40])[CH3:39].[K+].O1C[CH2:46][CH2:45][CH2:44]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH:18]12[NH:23][CH:21]([CH2:20][CH2:19]1)[CH2:22][C:16](=[C:7]1[C:6]3[CH:5]=[CH:4][CH:3]=[C:2]([NH:1][C:31]4[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=4)[C:15]=3[O:40][C:38]3[C:41]1=[CH:44][CH:45]=[CH:46][CH:39]=3)[CH2:17]2

Participants

9

Reactant 5

HCID 8028TetrahydrofuranHCID 122863-BromopyridineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23665647Potassium tert-butoxideHCID 57833604HCID 57833604, compound

Product 1

HCID 15986728HCID 15986728, compoundYield 12%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 1-[3-(4-aminoxanthen-9-ylidene)-8-azabicyclo[3.2.1]oct-8-yl]-2,2,2-trifluoro-ethanone 1l (100 mg, 0.25 mmol) in dioxane (6 mL) was added 3-bromopyridine (0.05 mL, 0.5 mmol), 1M potassium tert-butoxide in tetrahydrofuran (1.2 mL, 1.2 mmol), Pd2(dba)3 (9 mg, 0.0125 mmol) and Xanthphos (4.5 mg, 0.0125 mmol). The mixture was irradiated in a microwave reactor for 30 min at 120° C. The mixture was allowed to cool to rt, water was added, and the mixture was extracted with ethyl acetate. The organic phase was separated, dried over Na2SO4, filtered, and evaporated. The residue was purified via reverse phase chromatography to yield 15 mg (12%) of title compound 62 as a TFA salt.

Workup

  1. customThe mixture was irradiated in a microwave reactor for 30 min at 120° C
  2. extractionthe mixture was extracted with ethyl acetate
  3. customThe organic phase was separated
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified via reverse phase chromatography

Sources & evidence

ORD record
ord-945674106efd47caafc34aa450bd631b
Source dataset
uspto-grants-2009_09
Patent number
US07582650B2

Reaction notes

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