1,2-Dimethoxyethane → 8-(3,6-Dihydro-2H-pyran-4-yl)-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene

HRID 1629328Notes

Reaction equation

HRID 1629328 reaction equation
[O:1]1[CH2:6][CH:5]=[C:4](OS(C(F)(F)F)(=O)=O)[CH2:3][CH2:2]1.CC1(C)COB([C:22]2[CH:43]=[CH:42][C:25]3[C:26]4[N:30]([CH2:31][CH2:32][O:33][C:24]=3[CH:23]=2)[CH:29]=[C:28]([C:34]2[N:35]([CH:39]([CH3:41])[CH3:40])[N:36]=[CH:37][N:38]=2)[N:27]=4)OC1.C(=O)([O-])[O-].[Cs+].[Cs+].COCCOC>C(Cl)Cl.O>[O:1]1[CH2:6][CH:5]=[C:4]([C:22]2[CH:43]=[CH:42][C:25]3[C:26]4[N:30]([CH2:31][CH2:32][O:33][C:24]=3[CH:23]=2)[CH:29]=[C:28]([C:34]2[N:35]([CH:39]([CH3:41])[CH3:40])[N:36]=[CH:37][N:38]=2)[N:27]=4)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10796Cesium carbonateHCID 113567033,6-dihydro-2H-pyran-4-yl trifluoromethanesulfonateHCID 582047108-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene

Product 1

HCID 582046128-(3,6-Dihydro-2H-pyran-4-yl)-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azuleneYield 39.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of trifluoro-methanesulfonic acid 3,6-dihydro-2H-pyran-4-yl ester (125 mg, 0.54 mmol), 8-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene (200 mg, 0.491 mmol), PdCl2dppf.DCM (41 mg, 0.05 mmol, 10 mol %), cesium carbonate (400 mg, 1.23 mmol), DME (2 mL) and water (0.2 mL) was heated at 80° C. for 90 min. The cooled reaction mixture was diluted with DCM, filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 100% ethyl acetate in cyclohexane) to give 8-(3,6-Dihydro-2H-pyran-4-yl)-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene (73 mg, 39%). LCMS RT=4.36, [M+H]+=378.

Workup

  1. customThe cooled reaction mixture
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-013fa9a528584fb1988f17a50cbb2be1
Source dataset
uspto-grants-2014_07
Patent number
US08785626B2

Reaction notes

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