Diisopropylethylamine → (E)-2-Bromo-N-(2-methyl-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide

HRID 587301Notes

Reaction equation

HRID 587301 reaction equation
[Br:1][C:2]1[CH:10]=[C:9](/[CH:11]=[CH:12]/[CH:13]([C:18]2[CH:23]=[C:22]([Cl:24])[C:21]([Cl:25])=[C:20]([Cl:26])[CH:19]=2)[C:14]([F:17])([F:16])[F:15])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.O.N1(O)C2C=CC=C[C:31]=2N=N1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[F:63][C:64]([F:75])([F:74])[CH2:65][NH:66][C:67]([CH:69]([NH2:73])[CH:70](C)C)=[O:68].C(N(C(C)C)CC)(C)C>CC#N>[Br:1][C:2]1[CH:10]=[C:9](/[CH:11]=[CH:12]/[CH:13]([C:18]2[CH:23]=[C:22]([Cl:24])[C:21]([Cl:25])=[C:20]([Cl:26])[CH:19]=2)[C:14]([F:15])([F:16])[F:17])[CH:8]=[CH:7][C:3]=1[C:4]([NH:73][C:69]([CH3:70])([CH3:31])[C:67](=[O:68])[NH:66][CH2:65][C:64]([F:63])([F:74])[F:75])=[O:6]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27960291-Hydroxybenzotriazole hydrateHCID 86722549(E)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic acidHCID 86722620N-(2,2,2-trifluoroethyl) 1-amino-2-methyl-propanecarboxamide hydrochloride

Product 1

HCID 86722619(E)-2-Bromo-N-(2-methyl-1-oxo-1-((2,2,2-trifluoroethyl)amino)propan-2-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamideYield 55%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To (E)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic acid (200 mg, 0.409 mmol) in MeCN (5 mL) was added 1H-benzo[d][1,2,3]triazol-1-ol hydrate (63 mg, 0.411 mmol), HBTU (155 mg, 0.409 mmol), N-(2,2,2-trifluoroethyl) 1-amino-2-methyl-propanecarboxamide hydrochloride (180 mg, 0.816 mmol) and diisopropylethylamine (0.24 mL, 1.38 mmol). After 24 h the material was concentrated in vacuo. The crude product was purified by passing the crude reaction mixture through a silica frit and eluting with EtOAc/hexane (1:2). The recovered material was further purified by medium pressure chromatography on silica with EtOAc/hexane as the eluent to afford the title compound as a white foam (147 mg, 55%). Characterization data for this molecule is listed in Table 2.

Workup

  1. concentrationAfter 24 h the material was concentrated in vacuo
  2. customThe crude product was purified
  3. customreaction mixture through a silica frit
  4. washeluting with EtOAc/hexane (1:2)
  5. customThe recovered material was further purified by medium pressure chromatography on silica with EtOAc/hexane as the eluent

Sources & evidence

ORD record
ord-864db083d0e6404d8d3212efcf34f1e5
Source dataset
uspto-grants-2016_01
Patent number
US09226500B2

Reaction notes

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