Triethylamine → N-(1-(1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)ethyl)-2-methyl-4-(5-(3,4,5-tri-chlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzamide

HRID 1037047Notes

Reaction equation

HRID 1037047 reaction equation
[CH3:1][C:2]1[CH:10]=[C:9]([C:11]2[CH2:15][C:14]([C:20]3[CH:25]=[C:24]([Cl:26])[C:23]([Cl:27])=[C:22]([Cl:28])[CH:21]=3)([C:16]([F:19])([F:18])[F:17])[O:13][N:12]=2)[CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC.Cl.[NH2:61][CH:62]([C:64]1[CH:65]=[CH:66][C:67]2[C:71]([CH3:73])([CH3:72])[O:70][B:69]([OH:74])[C:68]=2[CH:75]=1)[CH3:63]>CN(C=O)C.CC(=O)OCC>[OH:74][B:69]1[C:68]2[CH:75]=[C:64]([CH:62]([NH:61][C:4](=[O:5])[C:3]3[CH:7]=[CH:8][C:9]([C:11]4[CH2:15][C:14]([C:20]5[CH:21]=[C:22]([Cl:28])[C:23]([Cl:27])=[C:24]([Cl:26])[CH:25]=5)([C:16]([F:18])([F:19])[F:17])[O:13][N:12]=4)=[CH:10][C:2]=3[CH3:1])[CH3:63])[CH:65]=[CH:66][C:67]=2[C:71]([CH3:72])([CH3:73])[O:70]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 866854502-Methyl-4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzoic acidHCID 866854936-(1-aminoethyl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol hydrochloride

Product 1

HCID 71576227N-(1-(1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)ethyl)-2-methyl-4-(5-(3,4,5-tri-chlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzamideYield 48.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-methyl-4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazol-3-yl)benzoic acid (150 mg, 0.33 mmol), HATU (188 mg, 0.495 mmol) and Et3N (0.15 mL, 0.99 mmol) in DMF (10 mL) was added 6-(1-aminoethyl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol hydrochloride (0.93 mmol). The mixture was stirred at rt overnight and EA (50 mL) was added. The mixture was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by prep-HPLC to give the title compound N-(1-(1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)ethyl)-2-methyl-4-(5-(3,4,5-tri-chlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzamide (103 mg; yield 18% over 5 steps) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 9.00 (s, 1H), 8.82 (d, J=7.6 Hz, 1H), 7.84 (s, 2H), 7.37-7.67 (m, 6H), 5.16 (m, 1H), 4.40 (d, J=18.0 Hz, 1H), 4.33 (d, J=18.0 Hz, 1H), 2.33 (s, 3H), 1.47-1.44 (m, 9H) ppm; HPLC purity: 99.88% at 220 nm and 99.77% at 254 nm; MS: m/z=639.8 (M+1, ESI+).

Workup

  1. washThe mixture was washed with brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-6e5bbb0baf444fda8a02ecc158c462b4
Source dataset
uspto-grants-2013_10
Patent number
US08546357B2

Reaction notes

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