Ethanol → HCID 136409082, compound

HRID 1622563Notes

Reaction equation

HRID 1622563 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[NH:19][C:18](=[O:20])[O:17][N:16]=2)=[CH:11][CH:10]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.CCN(C(C)C)C(C)C.C[CH2:43][OH:44].Cl.[F:46][C:47]([F:67])([F:66])[C:48]1[CH:53]=[CH:52][C:51]([C@@H:54]([C:56]2[C:61]([C:62]([F:65])([F:64])[F:63])=[CH:60][CH:59]=[CH:58][N:57]=2)[NH2:55])=[CH:50][CH:49]=1>C(Cl)Cl.O>[O:20]=[C:18]1[O:17][N:16]=[C:15]([C:12]2[CH:11]=[CH:10][C:9]([NH:8][C:43]([NH:55][C@@H:54]([C:51]3[CH:52]=[CH:53][C:48]([C:47]([F:67])([F:46])[F:66])=[CH:49][CH:50]=3)[C:56]3[C:61]([C:62]([F:63])([F:64])[F:65])=[CH:60][CH:59]=[CH:58][N:57]=3)=[O:44])=[CH:14][CH:13]=2)[NH:19]1

Participants

8

Reactant 5

HCID 702EthanolHCID 682631,1'-CarbonyldiimidazoleHCID 81531Diisopropylethylamine2×HCID 86687962(S)-(4-(Trifluoromethyl)phenyl)(3-(trifluoromethyl)pyridin-2-yl)methanamine HydrochlorideHCID 136409083HCID 136409083, compound

Product 1

HCID 136409082HCID 136409082, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

A 25 mL round-bottomed flask containing a solution of 3-(4-amino-phenyl)-1,2,4-oxadiazol-5(4H)-one 2,2,2-trifluoroacetate (0.107 g, 0.367 mmol) and CDI (0.140 g, 0.863 mmol) in anhydrous DCM (3.5 mL) was treated with DIPEA (0.200 mL, 1.150 mmol) and stirred for 3.5 h at rt. A solution of(S)-(4-(trifluoromethyl)phenyl)(3-(trifluoromethyl)pyridin-2-yl)methanamine hydrochloride (Intermediate 1) (0.118 g, 0.368 mmol) in anhydrous DCM (3.5 mL) was added followed by DIPEA (0.200 mL, 1.150 mmol), and the reaction mixture was stirred at rt for 12 h. The reaction mixture was then diluted with DCM (10 mL) and water (5 mL) and then absorbed onto a Varian Chem Elut (Diatomaceous Earth) cartridge. The organic filtrates were collected and concentrated to dryness. The resulting product was dissolved in DMSO/MeOH (1/1) (2.0 mL) and loaded on a Gilson HPLC system for purification using a MeCN/H2O 0.1% TFA gradient and Phenomenx Gemini Axia-5μ C-18 column (150×30 mm). The solvent was removed from the pure fractions in the GENEVAC and the residue was dried under high vacuum to yield the title compound as an amorphous off-white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 12.76 (s, 1H), 9.24 (s, 1H), 8.98 (d, J=3.9 Hz, 1H), 8.33-8.21 (m, 1H), 7.78-7.61 (m, 6H), 7.59-7.46 (m, 4H), 6.51 (d, J=8.4 Hz, 1H) MS (ESI pos. ion) m/z: 524.2 (M+H).

Workup

  1. stirringthe reaction mixture was stirred at rt for 12 h
  2. customabsorbed onto a Varian Chem Elut (Diatomaceous Earth) cartridge
  3. customThe organic filtrates were collected
  4. concentrationconcentrated to dryness
  5. dissolutionThe resulting product was dissolved in DMSO/MeOH (1/1) (2.0 mL)
  6. customloaded on a Gilson HPLC system for purification
  7. customThe solvent was removed from the pure fractions in the GENEVAC
  8. customthe residue was dried under high vacuum

Sources & evidence

ORD record
ord-10be57b7c2984c02976286378cfa5ba8
Source dataset
uspto-grants-2014_07
Patent number
US08778941B2

Reaction notes

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