Diisopropylethylamine → N-(2-(1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)propan-2-yl)-2-methyl-4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzamide

HRID 1037053Notes

Reaction equation

HRID 1037053 reaction equation
[NH2:1][C:2]([C:5]1[CH:6]=[CH:7][C:8]2[C:12]([CH3:14])([CH3:13])[O:11][B:10]([OH:15])[C:9]=2[CH:16]=1)([CH3:4])[CH3:3].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:50][C:51]1[CH:59]=[C:58]([C:60]2[CH2:64][C:63]([C:69]3[CH:74]=[C:73]([Cl:75])[C:72]([Cl:76])=[C:71]([Cl:77])[CH:70]=3)([C:65]([F:68])([F:67])[F:66])[O:62][N:61]=2)[CH:57]=[CH:56][C:52]=1[C:53](O)=[O:54]>C1COCC1.CC(=O)OCC>[OH:15][B:10]1[C:9]2[CH:16]=[C:5]([C:2]([NH:1][C:53](=[O:54])[C:52]3[CH:56]=[CH:57][C:58]([C:60]4[CH2:64][C:63]([C:69]5[CH:74]=[C:73]([Cl:75])[C:72]([Cl:76])=[C:71]([Cl:77])[CH:70]=5)([C:65]([F:68])([F:67])[F:66])[O:62][N:61]=4)=[CH:59][C:51]=3[CH3:50])([CH3:4])[CH3:3])[CH:6]=[CH:7][C:8]=2[C:12]([CH3:14])([CH3:13])[O:11]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 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 866854976-(2-aminopropan-2-yl)-3,3-dimethylbenzo[c][1,2]-oxaborol-1(3H)-ol

Product 1

HCID 71576286N-(2-(1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)propan-2-yl)-2-methyl-4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzamideYield 41.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6-(2-aminopropan-2-yl)-3,3-dimethylbenzo[c][1,2]-oxaborol-1(3H)-ol (100 mg), HATU (277 mg, 0.73 mmol) and DIPEA (0.2 mL, 1.1 mmol) in THF (5 mL) was added 2-methyl-4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzoic acid (80 mg, 0.37 mmol). The reaction mixture was stirred at rt overnight. EA was added and 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 final title compound N-(2-(1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)propan-2-yl)-2-methyl-4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzamide (100 mg; yield 38% over 3 steps) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 8.99 (s, 1H), 8.64 (s, 1H), 7.85 (s, 2H), 7.74 (s, 1H), 7.47-7.55 (m, 4H), 7.36 (d, J=8.4 Hz, 1H), 4.41 (d, J=18.4 Hz, 1H), 4.34 (d, J=18.4 Hz, 1H), 2.33 (s, 3H), 1.66 (s, 6H), 1.44 (s, 6H) ppm; HPLC purity: 99.29% at 220 nm and 99.63% at 254 nm; MS: m/z=653.8 (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-0f98f6a1ae2e4a729cd613c0185d25de
Source dataset
uspto-grants-2013_10
Patent number
US08546357B2

Reaction notes

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