Diisopropylethylamine → 3-amino-N-(5-chloro-2-methylbenzyl)isoxazole-5-carboxamide

HRID 1891411Notes

Reaction equation

HRID 1891411 reaction equation
[NH2:1][C:2]1[CH:6]=[C:5]([C:7]([OH:9])=O)[O:4][N:3]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[Cl:37][C:38]1[CH:39]=[CH:40][C:41]([CH3:46])=[C:42]([CH2:44][NH2:45])[CH:43]=1.C(N(CC)C(C)C)(C)C>CN(C=O)C.C(OCC)(=O)C.O>[NH2:1][C:2]1[CH:6]=[C:5]([C:7]([NH:45][CH2:44][C:42]2[CH:43]=[C:38]([Cl:37])[CH:39]=[CH:40][C:41]=2[CH3:46])=[O:9])[O:4][N:3]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 27576735-Chloro-2-methylbenzylamineHCID 552646873-Aminoisoxazole-5-carboxylic acid

Product 1

HCID 583322153-amino-N-(5-chloro-2-methylbenzyl)isoxazole-5-carboxamideYield 71.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-aminoisoxazole-5-carboxylic acid (492 mg, 3.84 mmol) in DMF (16 mL) was added benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (1.87 g, 4.22 mmol) at 0° C. The resulting solution was stirred for 5 min, after which time, 1-(5-chloro-2-methylphenyl)methanamine (598 mg, 3.84 mmol) and N,N-diisopropylethylamine (2.0 mL, 12 mmol) was added. The solution was stirred at room temperature for 0.5 h. The reaction solution was diluted with ethyl acetate and water, the organic layer was separated and dried over Na2SO4, filtered and concentrated. The residue was recrystallized with ethyl acetate and hexanes to give product (730 mg, 71%). LCMS calculated for C12H13ClN3O2(M+H)+: m/z=266.1.

Workup

  1. stirringThe solution was stirred at room temperature for 0.5 h
  2. customthe organic layer was separated
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was recrystallized with ethyl acetate and hexanes

Sources & evidence

ORD record
ord-5dbc5b1bf85b414a913153aa730ff024
Source dataset
uspto-grants-2013_08
Patent number
US08507541B2

Reaction notes

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