Morpholine → 4-(4-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-1-yl)methyl)pyridin-2-yl)morpholine

HRID 1475210Notes

Reaction equation

HRID 1475210 reaction equation
Cl[C:2]1[CH:7]=[C:6]([CH2:8][N:9]2[C:13]([CH3:14])=[N:12][C:11]([C:15]3[O:19][N:18]=[C:17]([C:20]4[CH:25]=[CH:24][C:23]([O:26][C:27]([F:30])([F:29])[F:28])=[CH:22][CH:21]=4)[N:16]=3)=[N:10]2)[CH:5]=[CH:4][N:3]=1.[NH:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1>CS(C)=O>[CH3:14][C:13]1[N:9]([CH2:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)[CH:7]=2)[N:10]=[C:11]([C:15]2[O:19][N:18]=[C:17]([C:20]3[CH:25]=[CH:24][C:23]([O:26][C:27]([F:30])([F:29])[F:28])=[CH:22][CH:21]=3)[N:16]=2)[N:12]=1

Participants

4

Reactant 2

HCID 8083MorpholineHCID 867119025-(1-((2-chloropyridin-4-yl)methyl)-5-methyl-1H-1,2,4-triazol-3-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole

Product 1

HCID 867119034-(4-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-1-yl)methyl)pyridin-2-yl)morpholineYield 63%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
130 °C

Procedure

5-(1-((2-Chloropyridin-4-yl)methyl)-5-methyl-1H-1,2,4-triazol-3-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole (50 mg, 0.115 mmol) and morpholine (100 mg, 1.15 mmol) were dissolved in DMSO (0.5 mL) in a sealed tube reaction vessel. The reaction was heated at 130° C. overnight and then cooled to RT. The reaction was then filtered and purified by prep-HPLC (MeCN/H2O 30%—MeCN 70% containing 0.1% TFA). The product was taken up in EtOAc (10 mL), washed with sat. NaHCO3 (10 mL), dried over Na2SO4, filtered, and concentrated to afford 4-(4-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-1-yl)methyl)pyridin-2-yl)morpholine as a yellow solid (35 mg, 63%). MS (ES+) C22H20F3N7O3 requires: 487. found 488 [M+H]+; 1H NMR (600 MHz, CDCl3) δ 8.28 (d, J=8.8 Hz, 2H), 8.18 (d, J=5.3 Hz, 1H), 7.34 (d, J=8.8 Hz, 2H), 6.44 (d, J=5.3 Hz, 1H), 6.37 (s, 1H), 5.37 (s, 2H), 3.82-3.77 (m, 4H), 3.51-3.45 (m, 4H), 2.55 (s, 3H).

Workup

  1. temperaturecooled to RT
  2. filtrationThe reaction was then filtered
  3. custompurified by prep-HPLC (MeCN/H2O 30%—MeCN 70% containing 0.1% TFA)
  4. washwashed with sat. NaHCO3 (10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-84632dbd9f994db9ac3eb087c3bf4994
Source dataset
uspto-grants-2015_04
Patent number
US09018380B2

Reaction notes

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