Pyridine → 3-{2-methoxy-4-[4-(3-perhydro-azepin-1-yl-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-phenyl}-4H-1,2,4-oxadiazol-5-one

HRID 2263439Notes

Reaction equation

HRID 2263439 reaction equation
O[CH2:2][CH2:3][CH2:4][C:5]1[N:6]=[C:7]([C:26]2[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][CH:27]=2)[S:8][C:9]=1[CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[NH:22][C:21](=[O:23])[O:20][N:19]=2)=[C:14]([O:24][CH3:25])[CH:13]=1.[N:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.[CH3:42]S(OS(C)(=O)=O)(=O)=O>C(#N)C>[CH3:25][O:24][C:14]1[CH:13]=[C:12]([O:11][CH2:10][C:9]2[S:8][C:7]([C:26]3[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:33])[F:34])=[CH:28][CH:27]=3)=[N:6][C:5]=2[CH2:4][CH2:3][CH2:2][N:36]2[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37][CH2:42]2)[CH:17]=[CH:16][C:15]=1[C:18]1[NH:22][C:21](=[O:23])[O:20][N:19]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 81560Methanesulfonic anhydrideHCID 1361499373-{4-[4-(3-hydroxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-methoxy-phenyl}-4H-[1,2,4]oxadiazol-5-one

Product 1

HCID 1361500063-{2-methoxy-4-[4-(3-perhydro-azepin-1-yl-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-phenyl}-4H-1,2,4-oxadiazol-5-one

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a mixture of 150 mg of 3-{4-[4-(3-hydroxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-methoxy-phenyl}-4H-[1,2,4]oxadiazol-5-one in 6 mL of acetonitrile were added 0.100 mL of pyridine and 0.200 mL of methanesulfonic anhydride. The resulting mixture was stirred at room temperature for 5 hour then 0.250 mL of hexamethyleneimine was added. The mixture was stirred at room temperature overnight and then concentrated under reduced pressure. The residue was purified by preparative HPLC on normal phase coupled to MS (gradient of methanol 5 in dichloromethane containing NH4OH), then precipitated from dichloromethane/pentane to give 26 mg of 3-{2-methoxy-4-[4-(3-perhydro-azepin-1-yl-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-phenyl}-4H-1,2,4-oxadiazol-5-one as a white solid.

Workup

  1. stirringThe mixture was stirred at room temperature overnight
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was purified by preparative HPLC on normal phase
  4. additioncoupled to MS (gradient of methanol 5 in dichloromethane containing NH4OH)
  5. customprecipitated from dichloromethane/pentane

Sources & evidence

ORD record
ord-b2bdec3045704600a56ea8fd239198b6
Source dataset
uspto-grants-2010_12
Patent number
US07851493B2

Reaction notes

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