Potassium Carbonate → 2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-8-[1-(2-methoxy-ethyl)-piperidin-4-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene

HRID 708255Notes

Reaction equation

HRID 708255 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].[CH3:36][O:37][CH2:38][CH2:39]Br.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]([CH2:39][CH2:38][O:37][CH3:36])[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 809722-Bromoethyl methyl etherHCID 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 582042082-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-8-[1-(2-methoxy-ethyl)-piperidin-4-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azuleneYield 70%

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 (300 mg, 0.59 mmol) in DMF (3.5 mL) was added 2-bromoethyl methyl ether (60 μl, 0.65 mmol) and potassium carbonate (285 mg, 2.07 mmol) and the reaction mixture stirred at 60° C. for 2 h. The reaction mixture was diluted with DCM and washed with saturated aqueous sodium bicarbonate, 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) followed by trituration in cyclohexane to give 511 (187 mg, 70%). LCMS: RT=3.42 min, [M+H]+=454. 1H NMR 400 MHz (DMSO-d6) δ: 8.23 (1H, d, J=8.19 Hz), 8.05 (1H, s), 7.04 (1H, dd, J=8.22, 1.79 Hz), 6.88 (1H, d, J=1.74 Hz), 5.77-5.76 (1H, m), 4.31 (2H, t, J=5.00 Hz), 3.44-3.34 (5H, m), 3.20 (3H, s), 2.93 (3H, d, J=10.98 Hz), 2.02 (2H, t, J=11.43 Hz), 1.71 (3H, m), 1.64-1.53 (2H, m), 1.50 (6H, d, J=6.58 Hz)

Workup

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

Sources & evidence

ORD record
ord-c484ca91cb584712994dc597aa41538b
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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