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

HRID 1037059Notes

Reaction equation

HRID 1037059 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]([OH:6])=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:62][CH2:63][C:64]1[CH:65]=[C:66]([F:76])[C:67]2[C:71]([CH3:73])([CH3:72])[O:70][B:69]([OH:74])[C:68]=2[CH:75]=1>CN(C=O)C>[F:76][C:66]1[C:67]2[C:71]([CH3:72])([CH3:73])[O:70][B:69]([OH:74])[C:68]=2[CH:75]=[C:64]([CH2:63][NH:62][C:4](=[O:6])[C:3]2[CH:7]=[CH:8][C:9]([C:11]3[CH2:15][C:14]([C:20]4[CH:25]=[C:24]([Cl:26])[C:23]([Cl:27])=[C:22]([Cl:28])[CH:21]=4)([C:16]([F:19])([F:18])[F:17])[O:13][N:12]=3)=[CH:10][C:2]=2[CH3:1])[CH:65]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)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 866855046-(aminomethyl)-4-fluoro-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol

Product 1

HCID 71576287N-((4-fluoro-1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)methyl)-2-methyl-4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzamideYield 40.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of crude 2-methyl-4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzoic acid (0.45 g, 1 mmol) in DMF (5 mL) at rt under N2 was added HBTU (0.76 g, 2 mmol), followed by DIPEA (0.39 g, 3 mmol). The reaction mixture was stirred at rt overnight. The reaction mixture was purified by chromatography over silica gel eluted with PE-DCM (1:1) to give an activated intermediate from acid, which was used directly to mix with 6-(aminomethyl)-4-fluoro-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol (0.3 g, 1.44 mmol) in 5 mL of DMF. The reaction mixture was stirred at rt overnight. The reaction was monitored by LC-MS. The reaction solution was purified by pre-HPLC to give the final title compound (260 mg, 40.4% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 9.31 (s, 1H), 8.97 (t, 1H), 7.86 (s, 2H), 7.63-7.62 (m, 2H), 7.53-7.51 (m, 2H), 7.24 (d, 1H), 4.50 (d, J=5.6 Hz, 2H), 4.43-4.31 (m, 2H) 2.42 (s, 3H) 1.53 (s, 6H) ppm; HPLC purity: 97.9% at 220 nm and 99.6 at 254 nm; MS (ESI+): m/z=643 (M+1).

Workup

  1. customThe reaction mixture was purified by chromatography over silica gel
  2. washeluted with PE-DCM (1:1)
  3. customto give an activated intermediate from acid, which
  4. stirringThe reaction mixture was stirred at rt overnight
  5. customThe reaction solution was purified by pre-HPLC

Sources & evidence

ORD record
ord-01cab681f939464cade7fb029bad6aab
Source dataset
uspto-grants-2013_10
Patent number
US08546357B2

Reaction notes

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