Water → HCID 86703997, compound

HRID 1773915Notes

Reaction equation

HRID 1773915 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)[C:3]=1[CH3:24].[Si]([O:32][CH2:33][CH2:34][C:35]#[C:36][B-](F)(F)F)(C(C)(C)C)(C)C.[K+].O.C([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:24][C:3]1[N:4]2[C:10]([CH:9]([O:12][CH:13]3[CH2:14][CH2:15][N:16]([CH3:19])[CH2:17][CH2:18]3)[C:8]3[CH:20]=[CH:21][CH:22]=[CH:23][C:7]=3[CH2:6][CH2:5]2)=[N:11][C:2]=1[C:36]#[C:35][CH2:34][CH2:33][OH:32]

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 23676307Potassium (4-{[tert-butyl(dimethyl)silyl]oxy}but-1-yn-1-yl)(trifluoro)borate(1-)HCID 86703973HCID 86703973, compound

Product 1

HCID 86703997HCID 86703997, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2-iodo-1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 133) (50 mg, 0.114 mmole) in THF (1 mL) are added potassium 4-tert-butyldimethylsilyloxybut-1-ynyltrifluoroborate (50 mg, 0.171 mmole), PdCl2(dppf)2 (8 mg, 0.011 mmole), water and Cs2CO3 (120 mg, 0.342 mmole). The flask is evacuated and filled with argon. The reaction mixture is heated at 80° C. for 24 hours. AcOEt and water are added, and the organic phase is washed with water, dried over MgSO4, filtered and the solvent removed under reduced pressure. The residue is purified by silica gel chromatography eluting with (CH2Cl2:MeOH) (98:2) to (90:10) then (CH2Cl2:MeOH:NH4OH) (9:1:0.1). The residue is dissolved in nBu4NF 1M in THF (0.5 mL) and the reaction mixture is stirred overnight at room temperature. Water is added and the aqueous phase is extracted with AcOEt. The organic phase is 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 (98:2:0.1) to (96.5:3.5:0.35) and the residue is submitted to a preparative thin-layer chromatography eluting with (CH2Cl2:MeOH:NH4OH) (9:1:1) to afford 4-[1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-but-3-yn-1-ol.

Workup

  1. customThe flask is evacuated
  2. additionfilled with argon
  3. additionAcOEt and water are added
  4. washthe organic phase is washed with water
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customthe solvent removed under reduced pressure
  8. customThe residue is purified by silica gel chromatography
  9. washeluting with (CH2Cl2:MeOH) (98:2) to (90:10)
  10. dissolutionThe residue is dissolved in nBu4NF 1M in THF (0.5 mL)
  11. additionWater is added
  12. extractionthe aqueous phase is extracted with AcOEt
  13. dry with materialThe organic phase is dried over magnesium sulphate
  14. filtrationfiltered
  15. customthe solvent is removed under reduced pressure
  16. customThe residue is pre-purified by silica gel chromatography
  17. washeluting with (CH2Cl2:MeOH:NH4OH) (9:1:1)

Sources & evidence

ORD record
ord-96b587f9f08b44eeaa5d37d290869567
Source dataset
uspto-grants-2016_02
Patent number
US09255101B2

Reaction notes

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