2-Pyridinemethanamine → N-(pyridin-2-ylmethyl)-2-(4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)acetamide

HRID 552859Notes

Reaction equation

HRID 552859 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([C:16]2[O:20][N:19]=[C:18]([C:21]3[CH:29]=[CH:28][CH:27]=[C:26]4[C:22]=3[CH:23]=[CH:24][N:25]4[CH2:30][C:31](O)=[O:32])[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:15])[C:11]([F:14])([F:13])[F:12].[CH:36]1[CH:37]=[CH:38][C:39]2[N:44](O)N=[N:42][C:40]=2[CH:41]=1.CCN=C=NCCCN(C)C.Cl.Cl.N1C=CC=CC=1CN.C([O-])(O)=O.[Na+]>CN(C=O)C>[N:42]1[CH:38]=[CH:37][CH:36]=[CH:41][C:40]=1[CH2:39][NH:44][C:31](=[O:32])[CH2:30][N:25]1[C:26]2[C:22](=[C:21]([C:18]3[N:17]=[C:16]([C:5]4[CH:6]=[CH:7][C:8]([O:9][CH:10]([CH3:15])[C:11]([F:14])([F:12])[F:13])=[C:3]([C:2]([F:1])([F:34])[F:35])[CH:4]=4)[O:20][N:19]=3)[CH:29]=[CH:28][CH:27]=2)[CH:23]=[CH:24]1

Participants

7

Reactant 5

HCID 195092-PyridinemethanamineHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 221413011-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride hydrochlorideHCID 59214325(4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)acetic acid

Product 1

HCID 59214364N-(pyridin-2-ylmethyl)-2-(4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)acetamideYield 89.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)acetic acid (150 mg) a HOBt(65 mg) in DMF (1.5 ml) was added EDCl/HCl (69 mg) at 0° C., followed by stirring at room temperature for 1 hour. After cooling to 0° C. again, 1-pyridin-2-ylmethanamine (39 mg) was added thereto, followed by stirring at room temperature for 15 hours. To the reaction solution was added a saturated aqueous NaHCO3 solution to complete the reaction. It was extracted with EtOAc, the organic layer was washed with saturated brine, dried over anhydrous MgSO4, and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:CH3OH=100:0 to 95:5) to obtain N-(pyridin-2-ylmethyl)-2-(4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)acetamide (157.8 mg) as a white solid. To a solution of N-(pyridin-2-ylmethyl)-2-(4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)acetamide (120 mg) in methylene chloride (2.4 ml) was added dropwise 10 equivalents of 4M HCl/dioxane, followed by stirring for 1 hour. The reaction mixture was concentrated under reduced pressure, and powdered/washed with IPE. The obtained solid was collected by filtration, and dried to obtain N-(pyridin-2-ylmethyl)-2-(4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)acetamide hydrochloride (126 mg) as a white solid.

Workup

  1. temperatureAfter cooling to 0° C. again
  2. stirringby stirring at room temperature for 15 hours
  3. customthe reaction
  4. extractionIt was extracted with EtOAc
  5. washthe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (chloroform:CH3OH=100:0 to 95:5)

Sources & evidence

ORD record
ord-d97ea92446774b40a57509eb3209d879
Source dataset
uspto-grants-2011_05
Patent number
US07951825B2

Reaction notes

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