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

HRID 1037084Notes

Reaction equation

HRID 1037084 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]([OH:25])=O)=[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.Cl.[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>[Cl:8][C:6]1[CH:5]=[C:4]([C:9]2([C:26]([F:28])([F:27])[F:29])[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]([NH:62][CH2:63][C:64]4[CH:65]=[CH:66][C:67]5[C:71]([CH3:73])([CH3:72])[O:70][B:69]([OH:74])[C:68]=5[CH:75]=4)=[O:25])=[CH:16][CH:15]=3)[CH2:10]2)[CH:3]=[C:2]([Cl:1])[CH:7]=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 715763408-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-((1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)methyl)indolizine-5-carboxamideYield 40.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 8-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)indolizine-5-carboxylic acid (23 mg, 0.052 mmol), HATU (30 mg, 0.078 mmol) and Et3N (0.02 mL, 0.104 mmol) in DMF (10 mL) was added 6-(aminomethyl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol hydrochloride (24 mg, 0.104 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 8-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-((1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)methyl)indolizine-5-carboxamide (13 mg, yield 40%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 9.50 (t, J=6.0 Hz, 1H), 9.05 (s, 1H), 8.19 (s, 1H), 7.83 (s, 1H), 7.67 (s, 3H), 7.47 (d, J=8.0 Hz, 1H), 7.40 (d, J=8.0 Hz, 1H), 7.21 (d, J=8.0 Hz, 1H), 7.17 (d, J=8.0 Hz, 1H), 7.11 (s, 1H), 6.94 (s, 1H), 4.57 (d, J=6.0 Hz, 2H), 4.48 (d, J=18.0 Hz, 1H), 4.38 (d, J=18.0 Hz, 1H), 1.44 (s, 6H) ppm; HPLC purity: 100.0% at 220 nm and 100.0% at 254 nm; MS: m/z=616.0 (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-6e309d358b804b89989f6d9ed87b327e
Source dataset
uspto-grants-2013_10
Patent number
US08546357B2

Reaction notes

Loading…