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-methyl-acetamide

HRID 1190710Notes

Reaction equation

HRID 1190710 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+].Br[CH2:43][C:44]([NH:46][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]([NH:46][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 154907452-Bromo-N-methylacetamideHCID 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 670505562-{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-methyl-acetamideYield 82.1%

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 (300 mg, 0.59 mmol) in THF (5 mL) was added potassium carbonate (285 mg, 2.10 mmol) followed by 2-bromo-N-methylacetamide (99 mg, 0.65 mmol). The reaction mixture was stirred for 3 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 triturated with diethyl ether to give 508 as a brown solid (226 mg, 82%). LCMS: RT=3.21 min, [M+H]+=467. 1H NMR δ (ppm) (DMSO-d6): 8.28 (1H, d, J=8.19 Hz), 8.10 (1H, s), 7.75-7.68 (1H, m), 7.10 (1H, dd, J=8.24, 1.81 Hz), 6.96 (1H, d, J=1.76 Hz), 5.86-5.77 (1H, m), 4.36 (2H, t, J=5.02 Hz), 3.42 (2H, t, J=5.03 Hz), 2.91-2.87 (4H, m), 2.64 (3H, d, J=4.74 Hz), 2.55-2.45 (1H, m), 2.19-2.17 (2H, m), 1.76-1.75 (4H, m), 1.55 (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 triturated with diethyl ether

Sources & evidence

ORD record
ord-39c7735bec3a416f9f08d0dbe95ac181
Source dataset
uspto-grants-2014_03
Patent number
US08673952B2

Reaction notes

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