Diisopropylethylamine → 4-(4-Chloro-phenyl)-5-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (3-methoxy-isoxazol-5-ylmethyl)-amide

HRID 1528405Notes

Reaction equation

HRID 1528405 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([O:14][CH2:15][C:16]([F:19])([F:18])[F:17])=[CH:12][N:11]=[C:10]([C:20]([OH:22])=O)[CH:9]=2)=[CH:4][CH:3]=1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.Cl.[CH3:55][O:56][C:57]1[CH:61]=[C:60]([CH2:62][NH2:63])[O:59][N:58]=1>CN(C)C=O>[CH3:55][O:56][C:57]1[CH:61]=[C:60]([CH2:62][NH:63][C:20]([C:10]2[CH:9]=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[C:13]([O:14][CH2:15][C:16]([F:19])([F:17])[F:18])=[CH:12][N:11]=2)=[O:22])[O:59][N:58]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 21292276(3-Methoxyisoxazol-5-yl)methanamine hydrochlorideHCID 66687043HCID 66687043, compound

Product 1

HCID 569296574-(4-Chloro-phenyl)-5-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (3-methoxy-isoxazol-5-ylmethyl)-amideYield 92.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(4-Chloro-phenyl)-5-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (100 mg, 0.3 mmol, example D) was dissolved in dimethylformamide (4 mL). To this stirred solution under argon was added in sequence 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (107 mg, 0.3 mmol), N,N-diisopropyl ethyl amine (0.26 mL, 1.5 mmol) and 3-methoxy-5-isoxazolemethanamine hydrochloride (55 mg, 0.3 mmol). The mixture was shaken for 16 h at room temperature, solvent was removed in vacuo (45° C.) and the residue was digested with dichloromethane (5 mL) and 2N NaOH (1.5 mL) for 5 min. The mixture was absorbed onto 10 g ChemElut (Varian) and eluted with dichloromethane (70 mL). Solvent was evaporated and the brown, oily residue (160 mg) was purified by gradient chromatography on silica with ethyl acetate/n-heptane to give the title compound as a white solid (122 mg, 92%), LC-MS (UV peak area/ESI) 93%, 442.0769 (M+H)+.

Workup

  1. customsolvent was removed in vacuo (45° C.)
  2. waitthe residue was digested with dichloromethane (5 mL) and 2N NaOH (1.5 mL) for 5 min
  3. customThe mixture was absorbed onto 10 g ChemElut (Varian)
  4. washeluted with dichloromethane (70 mL)
  5. customSolvent was evaporated
  6. customthe brown, oily residue (160 mg) was purified by gradient chromatography on silica with ethyl acetate/n-heptane

Sources & evidence

ORD record
ord-8f70b503a2644ff9bc5099bd32d9fb80
Source dataset
uspto-grants-2015_07
Patent number
US09090599B2

Reaction notes

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