Potassium Carbonate → 2-{4-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-piperidin-1-yl}-N,N-dimethyl-acetamide

HRID 708253Notes

Reaction equation

HRID 708253 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].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:43][C:44]([N:46]([CH3:48])[CH3:47])=[O:45]>C1COCC1.C(Cl)Cl.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][N:33]([CH2:43][C:44]([N:46]([CH3:48])[CH3:47])=[O:45])[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

7

Reactant 3

HCID 11430Potassium CarbonateHCID 758862-chloro-N,N-dimethylacetamideHCID 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 582038242-{4-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-piperidin-1-yl}-N,N-dimethyl-acetamideYield 43.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

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 TFA salt (386 mg, 0.76 mmol) in THF (5 mL) was added potassium carbonate (210 mg, 1.52 mmol) followed by 2-chloro-N,N-dimethylacetamide (102 mg, 0.84 mmol). The reaction mixture was stirred for 65 hours before being diluted with DCM and water. The organic layer was dried over anhydrous magnesium sulfate and concentrated in vacuo. The resulting residue was purified by silica gel flash chromatography (SiO2, gradient 0-3% methanol in DCM) then freeze-dried from methanol and water to give 509 as a white solid (158 mg, 43%). LCMS: RT=3.33 min, [M+H]+=481. 1H NMR δ (ppm) (DMSO-d6): 8.27 (1H, d, J=8.20 Hz), 8.09 (1H, d, J=0.59 Hz), 7.09 (1H, dd, J=8.25, 1.83 Hz), 6.93 (1H, d, J=1.77 Hz), 5.83-5.81 (1H, m), 4.35 (2H, t, J=5.02 Hz), 3.41 (2H, t, J=5.05 Hz), 3.15 (2H, s), 3.05 (3H, s), 2.93 (2H, d, J=10.95 Hz), 2.82 (3H, s), 2.48-2.44 (1H, m), 2.16-2.13 (2H, m), 1.81-1.70 (2H, m), 1.66-1.64 (2H, m), 1.54 (6H, d, J=6.59 Hz)

Workup

  1. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  2. concentrationconcentrated in vacuo
  3. customThe resulting residue was purified by silica gel flash chromatography (SiO2, gradient 0-3% methanol in DCM)
  4. dry with materialthen freeze-dried from methanol and water

Sources & evidence

ORD record
ord-a1383b790b824b5a91f1735b3180a355
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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