Ammonium formate → (S)-2-(3-amino-1H-1,2,4-triazol-5-yl)-1-(2-benzyl-4-(3-isopropoxy-4-methoxyphenyl)piperazin-1-yl)ethanone

HRID 1423167Notes

Reaction equation

HRID 1423167 reaction equation
[CH2:1]([C@H:8]1[CH2:13][N:12]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH:23]([CH3:25])[CH3:24])[CH:15]=2)[CH2:11][CH2:10][N:9]1[C:26](=[O:36])[CH2:27][C:28]1[N:32]=[C:31]([N+:33]([O-])=O)[NH:30][N:29]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])=O.[NH4+]>CO.[Pd]>[NH2:33][C:31]1[N:32]=[C:28]([CH2:27][C:26]([N:9]2[CH2:10][CH2:11][N:12]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH:23]([CH3:24])[CH3:25])[CH:15]=3)[CH2:13][C@@H:8]2[CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:36])[NH:29][N:30]=1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 135988895(S)-1-(2-benzyl-4-(3-isopropoxy-4-methoxyphenyl)piperazin-1-yl)-2-(5-nitro-1H-1,2,4-triazol-3-yl)ethanone2×

Product 1

HCID 58189009(S)-2-(3-amino-1H-1,2,4-triazol-5-yl)-1-(2-benzyl-4-(3-isopropoxy-4-methoxyphenyl)piperazin-1-yl)ethanone

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A solution of 1-[2(S)benzyl-4-(3-isopropoxy-4-methoxy-phenyl)-piperazin-1-yl]-2-(5-nitro-1H-[1,2,4]triazol-3-yl)-ethanone (Example 248, Compound 336) in MeOH (10 mL) was treated with 10% Palladium on Carbon (200 mg, 0.66 mmol) and ammonium formate (50 mg, 1.66 mmol). The reaction mixture was heated at 65 C for 1 h after which time the reaction was cooled and filtered with the aid of MeOH (20 mL) and EtOAc (20 mL). The organic portion was dried over MgSO4, filtered, and evaporated to an oil which was purified by silica gel flash chromatography with 5% then 10% MeOH/EtOAc as eluant to afford product as an oil. 1H NMR (CDCl3) 12.00-11.90 (br, 1H), 7.39-7.25 (m, 2H), 7.24-7.20 (m, 3H), 6.79 (d, J=8, 1H), 6.50-6.43 (m, 1H), 6.37-6.34 (m, 1H), 6.00-5.90 (br, 2H), 4.50-433 (m, 2H), 3.64 (s, 3H), 3.54-3.33 (m, 4H). 3.22-3.09 (m, 3H), 3.00-2.92 (m, 1H), 2.74-2.60 (m, 1H), 2.55-2.37 (m, 3H), 1.19 (d, J=6.4, 6H). LC/MS (Method B) 3.66 min, [M+1]+ 465. Potency class A.

Workup

  1. temperatureThe reaction mixture was heated at 65 C for 1 h after which time the reaction
  2. temperaturewas cooled
  3. filtrationfiltered with the aid of MeOH (20 mL) and EtOAc (20 mL)
  4. dry with materialThe organic portion was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated to an oil which
  7. customwas purified by silica gel flash chromatography with 5%
  8. custom10% MeOH/EtOAc as eluant to afford product as an oil
  9. customLC/MS (Method B) 3.66 min, [M+1]+ 465

Sources & evidence

ORD record
ord-7442bad2a04e45b698e5f05b53b58689
Source dataset
uspto-grants-2015_01
Patent number
US08927546B2

Reaction notes

Loading…