Triethylamine → N-((1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)methyl)-8-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)indolizine-5-carboxamide

HRID 1037091Notes

Reaction equation

HRID 1037091 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:26]([F:29])([F:28])[F:27])[O:13][N:12]=[C:11]([C:14]3[C:22]4[N:18]([CH:19]=[CH:20][CH:21]=4)[C:17]([C:23](O)=[O:24])=[CH:16][CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC.[ClH:61].[NH2:62][CH2:63][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>CN(C=O)C.CC(=O)OCC>[OH:74][B:69]1[C:68]2[CH:75]=[C:64]([CH2:63][NH:62][C:23]([C:17]3[N:18]4[C:22]([C:14]([C:11]5[CH2:10][C:9]([C:4]6[CH:3]=[C:2]([Cl:1])[C:7]([Cl:61])=[C:6]([Cl:8])[CH:5]=6)([C:26]([F:28])([F:29])[F:27])[O:13][N:12]=5)=[CH:15][CH:16]=3)=[CH:21][CH:20]=[CH:19]4)=[O:24])[CH:65]=[CH:66][C:67]=2[C:71]([CH3:73])([CH3:72])[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 86685457HCID 86685457, compoundHCID 866855228-[5-(Trifluoromethyl)-5-(3,5-dichlorophenyl)-2-isoxazoline-3-yl]indolizine-5-carboxylic acid

Product 1

HCID 71576342N-((1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)methyl)-8-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)indolizine-5-carboxamideYield 61%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of compound 8-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)indolizine-5-carboxylic acid (80 mg, 0.168 mmol), HATU (96 mg, 0.252 mmol) and Et3N (0.08 mL, 0.504 mmol) in DMF (15 mL) was added 6-(aminomethyl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-olhydrochloride (40 mg, 0.168 mmol). The mixture was stirred at rt overnight. EA (50 mL) 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 title compound N-((1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)methyl)-8-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)indolizine-5-carboxamide (54 mg, yield 61%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 9.50 (t, J=6.0 Hz, 1H), 9.04 (s, 1H), 8.18 (s, 1H), 7.89 (s, 2H), 7.68 (s, 1H), 7.49 (d, J=8.0 Hz, 1H), 7.41 (d, J=8.0 Hz, 1H), 7.19 (m, 2H), 7.11 (d, J=2.8 Hz,1H), 6.94 (t, J=2.8 Hz,1H), 4.57 (d, J=5.6 Hz, 2H), 4.48 (d, J=18.0 Hz, 1H), 4.41 (d, J=18.0 Hz, 1H), 1.44 (s, 6H) ppm; HPLC purity: 99.64% at 220 nm and 100.0% at 254 nm; MS: m/z=649.7 (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-b359d2a156f64a1fb8de9a79db50ed31
Source dataset
uspto-grants-2013_10
Patent number
US08546357B2

Reaction notes

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