Diisopropylethylamine → HCID 71576225, compound

HRID 1037038Notes

Reaction equation

HRID 1037038 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][CH2:65][C:66]1[CH:67]=[CH:68][C:69]2[C:73]([CH3:75])([CH3:74])[O:72][B:71]([OH:76])[C:70]=2[CH:77]=1>CN(C=O)C.O>[Cl:9][C:6]1[CH:5]=[C:4]([C:10]2([C:25]([F:28])([F:26])[F:27])[O:14][N:13]=[C:12]([C:15]3[CH:23]=[CH:22][C:18]([C:19]([NH:63][CH2:64][CH2:65][C:66]4[CH:67]=[CH:68][C:69]5[C:73]([CH3:74])([CH3:75])[O:72][B:71]([OH:76])[C:70]=5[CH:77]=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

7

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 866854826-(2-aminoethyl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol hydrochloride

Product 1

HCID 71576225HCID 71576225, compoundYield 50.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (390 mg, 0.9 mmol) and HATU (513 mg, 1.35 mmol) in DMF (18 mL), DIPEA (350 mg, 2.7 mmol) was added. The reaction mixture was stirred at rt for 10 min and crude 6-(2-aminoethyl)-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol hydrochloride (1 mmol) was added. The reaction mixture was continued to stir 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 prep-HPLC to give the final title compound 4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-(2-(1-hydroxy-3,3-dimethyl-1,3-dihydro-benzo[c][1,2]-oxaborol-6-yl)ethyl)-2-methylbenzamide (280 mg; yield 50.2%) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ 8.99 (s, 1H), 8.44 (t, J=6.0 Hz, 1H), 7.83 (d, J=6.5 Hz, 2H), 7.55-7.59 (m, 3H), 7.36-7.37 (m, 3H), 4.36 (d, J=18.5 Hz, 1 H), 4.34 (d, J=18.5 Hz, 1 H), 3.51 (q, J=7.5 Hz, 2H), 2.88 (t, J=7.5 Hz, 2H), 2.23 (s, 3 H), 1.45 (s, 6H) ppm;

Workup

  1. stirringto stir 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 prep-HPLC

Sources & evidence

ORD record
ord-daa1fdc1a7684da5847ef784e286bf31
Source dataset
uspto-grants-2013_10
Patent number
US08546357B2

Reaction notes

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