Potassium Carbonate → N-tert-Butyl-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}-acetamide

HRID 2386025Notes

Reaction equation

HRID 2386025 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+].[C:42]([NH:46][C:47](=[O:50])[CH2:48]Cl)([CH3:45])([CH3:44])[CH3:43]>C1COCC1.C(Cl)Cl.O>[C:42]([NH:46][C:47](=[O:50])[CH2:48][N:33]1[CH2:34][CH2:35][CH:30]([C:28]2[CH:27]=[CH:26][C:23]3[C:24]4[N:25]=[C:16]([C:15]5[N:11]([CH:8]([CH3:10])[CH3:9])[N:12]=[CH:13][N:14]=5)[S:17][C:18]=4[CH2:19][CH2:20][O:21][C:22]=3[CH:29]=2)[CH2:31][CH2:32]1)([CH3:45])([CH3:44])[CH3:43]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 222440N-tert-butyl-2-chloroacetamideHCID 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 67050586N-tert-Butyl-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}-acetamideYield 63.4%

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 (250 mg, 0.49 mmol) in THF (5 mL) was added potassium carbonate (136 mg, 0.98 mmol) followed by N-tert-butyl-2-chloroacetamide (81 mg, 0.54 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 510 as a beige solid (158 mg, 63%). LCMS: RT=3.67 min, [M+H]+=509. 1H NMR δ (ppm) (CDCl3): 8.34 (1 H, d, J=8.18 Hz), 7.93 (1 H, s), 7.10-7.06 (2 H, m), 6.96 (1 H, d, J=1.81 Hz), 5.92-5.91 (1H, m), 4.42 (2 H, t, J=5.03 Hz), 3.42 (2 H, t, J=5.05 Hz), 3.00-2.91 (4H, m), 2.61-2.48 (1 H, m), 2.35-2.24 (2 H, m), 1.96-1.87 (3 H, m), 1.83-1.71 (1H, m), 1.64 (6 H, d, J=6.63 Hz), 1.39 (9 H, s)

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-2556c2fd936f4a3aae512af5d8ece5f7
Source dataset
uspto-grants-2012_09
Patent number
US08263633B2

Reaction notes

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