Triethylamine → 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazol-3-yl)-N-((1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)-methyl)-2-methylbenzamide

HRID 1037010Notes

Reaction equation

HRID 1037010 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:24]([F:27])([F:26])[F:25])[O:13][N:12]=[C:11]([C:14]3[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[C:16]([CH3:23])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.CCN(CC)CC.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH2:60][CH2:61][C:62]1[CH:63]=[CH:64][C:65]2[C:69]([CH3:71])([CH3:70])[O:68][B:67]([OH:72])[C:66]=2[CH:73]=1>CC#N>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:24]([F:25])([F:26])[F:27])[O:13][N:12]=[C:11]([C:14]3[CH:22]=[CH:21][C:17]([C:18]([NH:60][CH2:61][C:62]4[CH:63]=[CH:64][C:65]5[C:69]([CH3:71])([CH3:70])[O:68][B:67]([OH:72])[C:66]=5[CH:73]=4)=[O:20])=[C:16]([CH3:23])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

6

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 231598114-(5-(3,5-Dichlorophenyl)-5-(tri fluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acidHCID 86685457HCID 86685457, compound

Product 1

HCID 715759424-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazol-3-yl)-N-((1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)-methyl)-2-methylbenzamideYield 21.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (1.65 g, 3.95 mmol) and Et3N (1.6 g, 15.8 mmol) in MeCN (35 ml) was stirred at rt for 5 min and then HATU (3 g, 7.9 mmol) was added. The mixture was stirred for 10 min prior to the addition of 6-(aminomethyl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol hydrochloride (906 mg, 4.74 mmol). And the resulting mixture was stirred at rt overnight. It was then concentrated under vacuum, and the residue was partitioned between 1N HCl and ethyl acetate. The organic layer separated was concentrated under vacuum, and the residue was purified by column chromatography and preparative HPLC to provide the product (500 mg, yield 21%). 1H NMR (300 MHz, DMSO-d6): δ 9.05 (s, 1H), 8.92 (s, 1H), 7.82 (s, 1H), 7.61 (m, 5H), 7.40 (m, 3H), 4.49 (d, 2H), 4.37 (d, 2H), 2.39 (s, 3H), 1.44 (s, 6H) ppm; HPLC purity: 97.4% at 220 nm and 98.1% at 254 nm; MS: m/z=591.3 (M+H, ESI+).

Workup

  1. stirringAnd the resulting mixture was stirred at rt overnight
  2. concentrationIt was then concentrated under vacuum
  3. customthe residue was partitioned between 1N HCl and ethyl acetate
  4. customThe organic layer separated
  5. concentrationwas concentrated under vacuum
  6. customthe residue was purified by column chromatography and preparative HPLC

Sources & evidence

ORD record
ord-1dde1a5fae3f40a380d3e0f6a297166a
Source dataset
uspto-grants-2013_10
Patent number
US08546357B2

Reaction notes

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