Potassium Carbonate → HCID 58203894, compound

HRID 708256Notes

Reaction equation

HRID 708256 reaction equation
OC(C(F)(F)F)=O.[CH:8]([N:11]1[C:15]([C:16]2[S:17][C:18]3[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]=4[C:24]=3[N:25]=2)=[N:14][CH:13]=[N:12]1)([CH3:10])[CH3:9].Br[CH2:37][CH2:38][O:39][CH:40]1[CH2:45][CH2:44][CH2:43][CH2:42][O:41]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(Cl)Cl>[CH:8]([N:11]1[C:15]([C:16]2[S:17][C:18]3[CH2:19][CH2:20][O:21][C:22]4[CH:29]=[C:28]([CH:30]5[CH2:35][CH2:34][N:33]([CH2:37][CH2:38][O:39][CH:40]6[CH2:45][CH2:44][CH2:43][CH2:42][O:41]6)[CH2:32][CH2:31]5)[CH:27]=[CH:26][C:23]=4[C:24]=3[N:25]=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 866523172-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene TFA salt

Product 1

HCID 58203894HCID 58203894, compoundYield 33.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene 375 (310 mg, 0.61 mmol) in DMF (3.5 mL) was added 2(2-bromoethoxy)tetrahydro-2H-pyran (0.1 mL, 0.67 mmol) and potassium carbonate (290 mg, 2.10 mmol) and the reaction mixture stirred at 60° C. for 16 h. The reaction mixture was diluted with DCM and washed with sodium bicarbonate (sat aq.) then water followed by brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0-10% MeOH 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-3-thia-1-aza-benzo[e]azulene (106 mg, 33%). LCMS: RT=3.71 min, [M+H]+=524 1H NMR 400 MHz (DMSO-d6) δ: 8.27 (1H, d, J=8.19 Hz), 8.09 (1H, d, J=0.58 Hz), 7.09 (1H, dd, J=8.26, 1.82 Hz), 6.92 (1H, d, J=1.78 Hz), 5.82-5.82 (1H, m), 4.58 (1H, t, J=3.52 Hz), 4.35 (2H, t, J=5.02 Hz), 3.75-3.74 (2H, m), 3.44-3.42 (4H, m), 2.99 (2H, t, J=10.97 Hz), 2.54 (2H, t, J=6.17 Hz), 2.47 (1H, s), 2.09 (2H, t, J=11.61 Hz), 1.79-1.55 (6H, m), 1.55 (6H, d, J=6.59 Hz), 1.52-1.43 (4H, m).

Workup

  1. washwashed with sodium bicarbonate (sat aq.)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f322a7d44e134f9887d93c9c0773a3a8
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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