Hydrochloric Acid → HCID 71575882, compound

HRID 1037008Notes

Reaction equation

HRID 1037008 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:49]([F:52])([F:51])[F:50])[O:38][N:37]=[C:36]([C:39]3[CH:47]=[CH:46][C:42]([C:43]([OH:45])=O)=[C:41]([CH3:48])[CH:40]=3)[CH2:35]2)[CH:29]=[C:30]([Cl:33])[C:31]=1[F:32].Cl.[NH2:54][CH2:55][C:56]1[CH:67]=[CH:66][C:59]2[B:60]([OH:65])[O:61][C:62]([CH3:64])([CH3:63])[C:58]=2[CH:57]=1.Cl>CC#N>[Cl:25][C:26]1[CH:27]=[C:28]([C:34]2([C:49]([F:51])([F:52])[F:50])[O:38][N:37]=[C:36]([C:39]3[CH:47]=[CH:46][C:42]([C:43]([NH:54][CH2:55][C:56]4[CH:67]=[CH:66][C:59]5[B:60]([OH:65])[O:61][C:62]([CH3:64])([CH3:63])[C:58]=5[CH:57]=4)=[O:45])=[C:41]([CH3:48])[CH:40]=3)[CH2:35]2)[CH:29]=[C:30]([Cl:33])[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 866854534-(5-(3,5-Dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid

Product 1

HCID 71575882HCID 71575882, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

HATU (350 mg, 0.92 mmol) was added to CH3CN (5 mL) at 0° C. After stirring for 5 min, the mixture was added to a solution of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (200 mg, 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 was stirred at rt for 2 h. The solution was acidified with HCl (1 N) and extracted with EA. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by prep-TLC (PE:EA=2:1) to give the final title compound (150 mg, yield 54%). 1H NMR (300 MHz, DMSO-d6): δ 8.98 (s, 1H), 8.92 (t, J=6.0 Hz, 1H), 7.78 (d, 2H), 7.62-7.58 (m, 3H), 7.48-7.45 (m, 1H), 7.33-7.27 (m, 2H), 4.49 (d, 2H), 4.39-4.25 (m, 2H), 2.36 (s, 3H), 1.42 (s, 6H); HPLC purity: 97.6% at 254 nm; MS: m/z=609 [M+H]+.

Workup

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

Sources & evidence

ORD record
ord-cab64c0ead4e41cda59b9101397891bd
Source dataset
uspto-grants-2013_10
Patent number
US08546357B2

Reaction notes

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