Potassium Carbonate → HCID 58204683, compound

HRID 1498356Notes

Reaction equation

HRID 1498356 reaction equation
FC(F)(F)C(O)=O.[CH:8]([N:11]1[C:15]([C:16]2[N:25]=[C:24]3[N:18]([CH2:19][CH2:20][O:21][C:22]4[CH:29]=[C:28]([CH:30]5[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]5)[CH:27]=[CH:26][C:23]=43)[CH:17]=2)=[N:14][CH:13]=[N:12]1)([CH3:10])[CH3:9].C(=O)([O-])[O-].[K+].[K+].Br[CH2:43][CH2:44][O:45][CH:46]1[CH2:51][CH2:50][CH2:49][CH2:48][O:47]1>CN(C=O)C.C(Cl)Cl>[CH:8]([N:11]1[C:15]([C:16]2[N:25]=[C:24]3[N:18]([CH2:19][CH2:20][O:21][C:22]4[CH:29]=[C:28]([CH:30]5[CH2:35][CH2:34][N:33]([CH2:43][CH2:44][O:45][CH:46]6[CH2:51][CH2:50][CH2:49][CH2:48][O:47]6)[CH2:32][CH2:31]5)[CH:27]=[CH:26][C:23]=43)[CH:17]=2)=[N:14][CH:13]=[N:12]1)([CH3:10])[CH3:9]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 866212-(2-Bromoethoxy)tetrahydro-2H-pyranHCID 670507222-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene trifluoroacetic acid salt

Product 1

HCID 58204683HCID 58204683, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred suspension of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene trifluoro acetate (300 mg, 0.61 mmol) in DMF (3.5 mL) was added potassium carbonate (290 mg, 2.1 mmol) and 2-(2-bromoethoxy)tetrahydro-2H-pyran and the mixture heated at 60° C. for 18 h before being diluted with DCM. The resultant solution was washed with saturated aqueous sodium hydrogen carbonate, water and then brine before being dried (MgSO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 8% methanol in DCM) to give 2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-8-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-piperidin-4-yl}-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene as a cream solid (147 mg, 48%). 1H NMR 400 MHz (CDCl3) δ: 8.44 (1 H, d, J=8.29 Hz), 7.87 (1 H, s), 7.63 (1 H, s), 7.04 (1 H, dd, J=8.33, 1.81 Hz), 6.92 (1 H, d, J=1.75 Hz), 6.01-6.00 (1 H, m), 4.63 (1 H, t, J=3.54 Hz), 4.46-4.45 (4 H, m), 3.92-3.91 (2 H, m), 3.65 (1 H, m), 3.57-3.49 (1 H, m), 3.15 (2 H, m), 2.73 (2 H, m), 2.53 (1 H, m), 2.25 (2 H, m), 1.87 (5 H, m), 1.73-1.69 (3 H, m), 1.60 (8 H, m).

Workup

  1. washThe resultant solution was washed with saturated aqueous sodium hydrogen carbonate, water
  2. dry with materialbrine before being dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ff5ce59a40344349832a7ee6cefe0605
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

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