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 2244649Notes

Reaction equation

HRID 2244649 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.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 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 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) and HOBt (65 mg) in DMF (1.5 ml) was added EDCI/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-73c89ef0035d43e8989c97e4c1cdf1b2
Source dataset
uspto-grants-2010_03
Patent number
US07678820B2

Reaction notes

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