Potassium Carbonate → 2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-9-(1-(2-methoxyethyl)piperidin-4-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

HRID 1629315Notes

Reaction equation

HRID 1629315 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][CH3:46]>CN(C=O)C.C(Cl)Cl>[CH:8]([N:11]1[C:15]([C:16]2[N:25]=[C:24]3[C:23]4[CH:26]=[CH:27][C:28]([CH:30]5[CH2:35][CH2:34][N:33]([CH2:43][CH2:44][O:45][CH3:46])[CH2:32][CH2:31]5)=[CH:29][C:22]=4[O:21][CH2:20][CH2:19][N:18]3[CH:17]=2)=[N:14][CH:13]=[N:12]1)([CH3:10])[CH3:9]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 809722-Bromoethyl methyl etherHCID 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 582043602-(1-isopropyl-1H-1,2,4-triazol-5-yl)-9-(1-(2-methoxyethyl)piperidin-4-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineYield 48%

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-1,3a-diaza-benzo[e]azulene trifluoroacetic acid salt (300 mg, 0.61 mmol) in DMF (3.5 mL) were added potassium carbonate (290 mg, 2.10 mmol) and 1-bromo-2-methoxy-ethane (93 mg, 0.67 mmol). The resultant reaction mixture was stirred at 60° C. for 4 hours before being cooled to RT and diluted with DCM. The mixture was washed sequentially with sodium hydrogen carbonate solution (sat. aq.), water and brine then dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by flash column chromatography (SiO2, gradient 0-8% MeOH in DCM) and triturated with petroleum ether to afford 286 as a white solid (127 mg, 0.29 mmol, 48%). LCMS: RT=3.02 min, [M+H]+=437. 1H NMR δ (ppm)(DMSO-d6): 8.28 (1 H, d, J=8.28 Hz), 7.86 (1 H, d, J=0.62 Hz), 7.85 (1 H, s), 7.01 (1 H, dd, J=8.36, 1.77 Hz), 6.85 (1 H, d, J=1.72 Hz), 5.90-5.80 (1 H, m), 4.45 (4 H, m), 3.40 (2 H, t, J=5.89 Hz), 3.20 (3 H, s), 2.93 (2 H, d, J=11.11 Hz), 2.01 (2 H, dd, J=12.41, 10.21 Hz), 1.70 (2 H, d, J=12.52 Hz), 1.58 (2 H, ddd, J=24.42, 12.21, 3.61 Hz), 1.44 (6 H, d, J=6.60 Hz). 3H obscured by solvent.

Workup

  1. customThe resultant reaction mixture
  2. temperaturebefore being cooled to RT
  3. washThe mixture was washed sequentially with sodium hydrogen carbonate solution (sat. aq.), water and brine
  4. dry with materialthen dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe resultant residue was purified by flash column chromatography (SiO2, gradient 0-8% MeOH in DCM)
  7. customtriturated with petroleum ether

Sources & evidence

ORD record
ord-8f9d5328930746108ae6a00abf84f6e1
Source dataset
uspto-grants-2014_07
Patent number
US08785626B2

Reaction notes

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