Potassium Fluoride → 4-(1-methylpiperidin-4-yloxy)-2-pyridin-2-yl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene

HRID 1773868Notes

Reaction equation

HRID 1773868 reaction equation
I[C:2]1[N:11]=[C:10]2[N:4]([CH2:5][CH2:6][C:7]3[CH:23]=[CH:22][CH:21]=[CH:20][C:8]=3[CH:9]2[O:12][CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)[CH:3]=1.C([Sn](CCCC)(CCCC)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=1)CCC.[F-].[K+]>C1(C)C=CC=CC=1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:19][N:16]1[CH2:17][CH2:18][CH:13]([O:12][CH:9]2[C:8]3[CH:20]=[CH:21][CH:22]=[CH:23][C:7]=3[CH2:6][CH2:5][N:4]3[C:10]2=[N:11][C:2]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=2)=[CH:3]3)[CH2:14][CH2:15]1

Participants

7

Reactant 3

HCID 522689Potassium FluorideHCID 6077842-(Tributylstannyl)pyridineHCID 726957782-iodo-4-(1-methyl piperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene

Product 1

HCID 867039554-(1-methylpiperidin-4-yloxy)-2-pyridin-2-yl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-iodo-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 2A) (50 mg, 0.12 mmoles) in toluene (500 μL) in a screw-capped vial under argon are added 2-(tributylstannyl)pyridine (77 μL, 0.24 mmole), tetrakis(triphenylphosphine)palladium(0) (14 mg, 12 μmole). The reaction mixture is heated at 100° C. overnight. A solution of 10% KF in water is added, and the aqueous phase is extracted three times with CH2Cl2. The organic phase is washed with a solution of 10% KF in water, brine, dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure. The residue is pre-purified by silica gel chromatography using (CH2Cl2:MeOH:NH4OH) as eluent with a gradient from (99:1:0.1) to (95:5:0.5) and the residue is submitted to a preparative thin-layer chromatography eluting with (CH2Cl2:MeOH:NH4OH) (9:1:1) to afford 4-(1-methylpiperidin-4-yloxy)-2-pyridin-2-yl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene.

Workup

  1. extractionthe aqueous phase is extracted three times with CH2Cl2
  2. washThe organic phase is washed with a solution of 10% KF in water, brine
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. customthe solvent is removed under reduced pressure
  6. customThe residue is pre-purified by silica gel chromatography
  7. washeluting with (CH2Cl2:MeOH:NH4OH) (9:1:1)

Sources & evidence

ORD record
ord-ff0d2fea893947aeb3acbc88148fdfae
Source dataset
uspto-grants-2016_02
Patent number
US09255101B2

Reaction notes

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