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

HRID 2385992Notes

Reaction equation

HRID 2385992 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].[CH:36]([S:38]([CH3:41])(=[O:40])=[O:39])=[CH2:37].C(Cl)Cl.CO>O.C(O)C>[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]([CH2:37][CH2:36][S:38]([CH3:41])(=[O:40])=[O:39])[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 4

HCID 887MethanolHCID 6344DichloromethaneHCID 19354Methyl vinyl sulfoneHCID 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 582042212-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-8-[1-(2-methanesulfonyl-ethyl)-piperidin-4-yl]-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azuleneYield 71%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

Following the procedure for 320, 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 TFA salt 375 and methyl vinyl sulfone were reacted, with added DCM to aid dissolution. Addition of a mixture of methanol, ethanol and water followed by removal in vacuo of the DCM precipitated the product from the reaction mixture. The resulting solid was collected by filtration to give 476 as an off-white solid (175 mg, 71%). LCMS: RT=3.30 min, [M+H]+=502. 1H NMR δ (ppm) (DMSO-d6): 8.23 (1 H, d, J=8.20 Hz), 8.05 (1 H, s), 7.05 (1 H, dd, J=8.25, 1.78 Hz), 6.89 (1 H, d, J=1.74 Hz), 5.82-5.72 (1 H, m), 4.33-4.27 (2 H, m), 3.37 (2 H, t, J=5.06 Hz), 3.02 (3 H, s), 2.97 (2 H, s), 2.70 (2H, s), 2.03 (2 H, s), 1.75 (2 H, d, J=12.38 Hz), 1.67-1.55 (2 H, m), 1.50 (6 H, d, J=6.59 Hz). 3 Protons obscured by solvent peaks

Workup

  1. dissolutiondissolution
  2. customfollowed by removal in vacuo of the DCM
  3. customprecipitated the product from the reaction mixture
  4. filtrationThe resulting solid was collected by filtration

Sources & evidence

ORD record
ord-20d1e1752ab9464da6a9f48eaa94335f
Source dataset
uspto-grants-2012_09
Patent number
US08263633B2

Reaction notes

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