Hydrochloric Acid → 5-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-((1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-5-yl)methyl)indolizine-8-carboxamide

HRID 1037095Notes

Reaction equation

HRID 1037095 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl:25][C:26]1[CH:27]=[C:28]([C:34]2([C:51]([F:54])([F:53])[F:52])[O:38][N:37]=[C:36]([C:39]3[N:40]4[C:44]([C:45]([C:48](O)=[O:49])=[CH:46][CH:47]=3)=[CH:43][CH:42]=[CH:41]4)[CH2:35]2)[CH:29]=[C:30]([Cl:33])[C:31]=1[F:32].Cl.[NH2:56][CH2:57][C:58]1[CH:69]=[CH:68][C:61]2[B:62]([OH:67])[O:63][C:64]([CH3:66])([CH3:65])[C:60]=2[CH:59]=1.Cl>CC#N>[Cl:33][C:30]1[CH:29]=[C:28]([C:34]2([C:51]([F:53])([F:54])[F:52])[O:38][N:37]=[C:36]([C:39]3[N:40]4[C:44]([C:45]([C:48]([NH:56][CH2:57][C:58]5[CH:69]=[CH:68][C:61]6[B:62]([OH:67])[O:63][C:64]([CH3:66])([CH3:65])[C:60]=6[CH:59]=5)=[O:49])=[CH:46][CH:47]=3)=[CH:43][CH:42]=[CH:41]4)[CH2:35]2)[CH:27]=[C:26]([Cl:25])[C:31]=1[F:32]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86685451HCID 86685451, compoundHCID 866855275-(5-(3,5-Dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)indolizine-8-carboxylic acid

Product 1

HCID 715765255-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-((1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-5-yl)methyl)indolizine-8-carboxamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

HATU (350 mg, 0.92 mmol) can be added to CH3CN (5 mL) at 0° C. After stirring for 5 min, the mixture can be added to a solution of 5-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)indolizine-8-carboxylic acid (0.46 mmol), 5-(aminomethyl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol hydrochloride (157 mg, 0.69 mmol), and TEA (186 mg, 1.83 mmol) in CH3CN (8 mL). Then the solution can be stirred at rt for 2 h. The solution can be acidified with HCl (1 N) and extracted with EA. The combined organic layers can be washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue can be purified by prep-TLC to give the final title compound.

Workup

  1. stirringThen the solution can be stirred at rt for 2 h
  2. extractionextracted with EA
  3. washThe combined organic layers can be washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue can be purified by prep-TLC

Sources & evidence

ORD record
ord-f57fde1e112f4daeb5b0ec7aea9ad374
Source dataset
uspto-grants-2013_10
Patent number
US08546357B2

Reaction notes

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