Diisopropylethylamine → HCID 71575945, compound

HRID 1037019Notes

Reaction equation

HRID 1037019 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2([C:25]([F:28])([F:27])[F:26])[O:14][N:13]=[C:12]([C:15]3[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[C:17]([CH3:24])[CH:16]=3)[CH2:11]2)[CH:5]=[C:6]([Cl:9])[C:7]=1[F:8].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl.[NH2:63][CH2:64][C:65]1[CH:66]=[CH:67][C:68]2[C:72]([CH3:74])([CH3:73])[O:71][B:70]([OH:75])[C:69]=2[CH:76]=1>CN(C=O)C.CC(=O)OCC.O>[Cl:9][C:6]1[CH:5]=[C:4]([C:10]2([C:25]([F:26])([F:27])[F:28])[O:14][N:13]=[C:12]([C:15]3[CH:23]=[CH:22][C:18]([C:19]([NH:63][CH2:64][C:65]4[CH:66]=[CH:67][C:68]5[C:72]([CH3:74])([CH3:73])[O:71][B:70]([OH:75])[C:69]=5[CH:76]=4)=[O:21])=[C:17]([CH3:24])[CH:16]=3)[CH2:11]2)[CH:3]=[C:2]([Cl:1])[C:7]=1[F:8]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 866854534-(5-(3,5-Dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acidHCID 86685457HCID 86685457, compound

Product 1

HCID 71575945HCID 71575945, compoundYield 61.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (3.6 g, 8.3 mmol) and HATU (5.24 g, 13.8 mmol) in DMF (25 mL) was added DIPEA (3.3 mL, 18.4 mmol). The reaction mixture was stirred at rt for 10 min and 6-(aminomethyl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol hydrochloride (2.1 g, 9.2 mmol) was added. The reaction mixture was stirred overnight. Water was added and the mixture was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography over silica gel eluted with PE:EA (3:1 to 1:1) to give the final title compound 4-(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-6-yl)methyl)-2-methylbenzamide (3.1 g; yield 61%) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ 9.08 (s, 1H), 8.94 (t, J=6.0 Hz, 1H), 7.84 (d, J=6.5 Hz, 2H), 7.66-7.62 (m, 3H), 7.53-7.43 (m, 3H), 4.49 (d, J=6.0 Hz, 2H), 4.39 (d, J=18.5 Hz, 1H), 4.36 (d, J=18.5 Hz, 1 H), 2.42 (s, 3 H), 1.47 (s, 6H) ppm; HPLC purity: 100% at 220 nm and 99.75% at 254 nm; MS: m/z=608.8 (M+1, ESI+).

Workup

  1. stirringThe reaction mixture was stirred overnight
  2. extractionthe mixture was extracted three times with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography over silica gel
  8. washeluted with PE

Sources & evidence

ORD record
ord-d6aa66c3e5424fe28ba74efab9512f3d
Source dataset
uspto-grants-2013_10
Patent number
US08546357B2

Reaction notes

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