Triethylamine → 3-(2-methoxy-4-{2-(4-trifluoromethyl-phenyl)-4-[(3,3,3-trifluoro-propylamino)-methyl]-thiazol-5-ylmethoxy}-phenyl)-4H-[1,2,4]oxadiazol-5-one

HRID 2263412Notes

Reaction equation

HRID 2263412 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:25]=[CH:26][C:27]=1[C:28]1[NH:32][C:31](=[O:33])[O:30][N:29]=1)[O:6][CH2:7][C:8]1[S:12][C:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)=[N:10][C:9]=1[CH:23]=O.C(N(CC)CC)C.Cl.[F:42][C:43]([F:48])([F:47])[CH2:44][CH2:45][NH2:46].[BH4-].[Na+]>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([O:6][CH2:7][C:8]2[S:12][C:11]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:20])[F:21])=[CH:15][CH:14]=3)=[N:10][C:9]=2[CH2:23][NH:46][CH2:45][CH2:44][C:43]([F:48])([F:47])[F:42])[CH:25]=[CH:26][C:27]=1[C:28]1[NH:32][C:31](=[O:33])[O:30][N:29]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 252105053,3,3-Trifluoropropylamine hydrochlorideHCID 136149986HCID 136149986, compound

Product 1

HCID 1361499463-(2-methoxy-4-{2-(4-trifluoromethyl-phenyl)-4-[(3,3,3-trifluoro-propylamino)-methyl]-thiazol-5-ylmethoxy}-phenyl)-4H-[1,2,4]oxadiazol-5-oneYield 18%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a suspension of 30 mg of 5-[3-methoxy-4-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-phenoxymethyl]-2-(4-trifluoromethyl-phenyl)-thiazole-4-carbaldehyde in 1.5 mL of methanol were added 0.018 mL of triethylamine, 10 mg of 3,3,3-trifluoro-propylamine hydrochloride and 0.5 g of 4 Å powdered molecular sieves. The resulting mixture was stirred at room temperature for 1 h then 2.4 mg of sodium borohydride was added. After stirring at room temperature for 45 minutes, the reaction mixture was concentrated under reduced pressure. The crude product was purified by preparative thin layer chromatography on silica gel (dichloromethane 90/methanol 10/water 1/acetic acid 1) followed by azeotropal removal of traces of acetic acid with cyclohexane to give 6.5 mg of 3-(2-methoxy-4-{2-(4-trifluoromethyl-phenyl)-4-[(3,3,3-trifluoro-propylamino)-methyl]-thiazol-5-ylmethoxy}-phenyl)-4H-[1,2,4]oxadiazol-5-one as a white solid.

Workup

  1. stirringAfter stirring at room temperature for 45 minutes
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. customThe crude product was purified by preparative thin layer chromatography on silica gel (dichloromethane 90/methanol 10/water 1/acetic acid 1)
  4. customfollowed by azeotropal removal of traces of acetic acid with cyclohexane

Sources & evidence

ORD record
ord-c774b45ead2841a9b0c84ef51fdbebc6
Source dataset
uspto-grants-2010_12
Patent number
US07851493B2

Reaction notes

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