Diisopropylethylamine → 5-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophene-2-carboxylic acid [(2,2,2-trifluoro-ethylcarbamoyl)-methyl]-amide

HRID 242406Notes

Reaction equation

HRID 242406 reaction equation
C[CH2:2][N:3](C(C)C)C(C)C.FC(F)(F)C([O-])=O.[F:17][C:18]([F:26])([F:25])[CH2:19][NH:20][C:21]([NH2+]C)=[O:22].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[Cl:60][C:61]1[CH:62]=[C:63]([C:68]2([C:82]([F:85])([F:84])[F:83])[O:72][N:71]=[C:70]([C:73]3[S:77][C:76]([C:78](O)=[O:79])=[C:75]([CH3:81])[CH:74]=3)[CH2:69]2)[CH:64]=[C:65]([Cl:67])[CH:66]=1>ClCCl>[F:26][C:18]([F:17])([F:25])[CH2:19][NH:20][C:21]([CH2:2][NH:3][C:78]([C:76]1[S:77][C:73]([C:70]2[CH2:69][C:68]([C:63]3[CH:62]=[C:61]([Cl:60])[CH:66]=[C:65]([Cl:67])[CH:64]=3)([C:82]([F:85])([F:84])[F:83])[O:72][N:71]=2)=[CH:74][C:75]=1[CH3:81])=[O:79])=[O:22]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 674288635-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophene-2-carboxylic acidHCID 86658040(2,2,2-Trifluoro-ethylcarbamoyl)-methyl-ammonium trifluoroacetate

Product 1

HCID 717654185-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophene-2-carboxylic acid [(2,2,2-trifluoro-ethylcarbamoyl)-methyl]-amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

DIPEA (0.246 ml) is added to a solution of (2,2,2-trifluoro-ethylcarbamoyl)-methyl-ammonium trifluoroacetate (0.170 g, Example 4, step B), PYBOP (0.270 g), and 5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophene-2-carboxylic acid (0.2 g) in dichloromethane (3 ml) at 0° C. After 30 minutes at room temperature the reaction is quenched with water and extracted three times with dichloromethane. The combined organic phases are washed with a saturated aqueous solution of NaCl and a saturated aqueous solution of NaHCO3, dried over Na2SO4 and concentrated in vacuo. The crude product is purified on a semi-preparative reversed phase HPLC to yield 5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophene-2-carboxylic acid [(2,2,2-trifluoro-ethylcarbamoyl)-methyl]-amide (8.73 g) as a beige foam. MS (HPLC/MS): 562 (MH+). Retention time: 3.94 min.

Workup

  1. customAfter 30 minutes at room temperature the reaction is quenched with water
  2. extractionextracted three times with dichloromethane
  3. washThe combined organic phases are washed with a saturated aqueous solution of NaCl
  4. dry with materiala saturated aqueous solution of NaHCO3, dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product is purified on a semi-preparative reversed phase HPLC

Sources & evidence

ORD record
ord-268876e34b95438dbebb4c9599ca8973
Source dataset
uspto-grants-2014_02
Patent number
US08653116B2

Reaction notes

Loading…