Diisopropylethylamine → 1-([4-[5-(3,5-Dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl]carbonyl)-3-(3,3,3-trifluoropropyl)imidazolidin-4-one

HRID 63880Notes

Reaction equation

HRID 63880 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](O)=[O:20])=[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.[F:62][C:63]([F:73])([F:72])[CH2:64][CH2:65][N:66]1[C:70](=[O:71])[CH2:69][NH:68][CH2:67]1>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2([C:25]([F:27])([F:28])[F:26])[O:14][N:13]=[C:12]([C:15]3[CH:23]=[CH:22][C:18]([C:19]([N:68]4[CH2:69][C:70](=[O:71])[N:66]([CH2:65][CH2:64][C:63]([F:62])([F:72])[F:73])[CH2:67]4)=[O:20])=[C:17]([CH3:24])[CH:16]=3)[CH2:11]2)[CH:5]=[C:6]([Cl:9])[C:7]=1[F:8]

Participants

6

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 832545243-(3,3,3-Trifluoropropyl)imidazolidin-4-oneHCID 866854534-(5-(3,5-Dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid

Product 1

HCID 1180470691-([4-[5-(3,5-Dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl]carbonyl)-3-(3,3,3-trifluoropropyl)imidazolidin-4-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Into a 50-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed N,N-dimethylformamide (2 mL), 4-[5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylbenzoic acid (50 mg, 0.11 mmol, 1.00 equiv), HATU (174 mg, 0.46 mmol, 4.00 equiv), DIEA (60 mg, 0.46 mmol, 4.00 equiv), 3-(3,3,3-trifluoropropyl)imidazolidin-4-one (25 g, 137.25 mmol, 1.00 equiv). The resulting solution was stirred for 2 h at room temperature. The crude product was purified by Prep-HPLC. This resulted in 22.1 mg (32%) of 1-([4-[5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl]carbonyl)-3-(3,3,3-trifluoropropyl)imidazolidin-4-one as a white solid. 641 [Ms+CH3CN+H]+; (300 MHz, CD3OD, ppm): δ7.77-7.64 (m, 4H), 7.45-7.28 (m, 1H), 5.12-4.69 (m, 1H), 4.32-4.22 (m, 1H), 4.08-4.01 (m, 1H), 3.87-3.54 (m, 2H), 3.14-2.87 (m, 3H), 2.70-2.31 (m, 4H).

Workup

  1. customInto a 50-mL round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. customThe crude product was purified by Prep-HPLC
  4. customThis resulted in 22.1 mg (32%) of 1-([4-[5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl]carbonyl)-3-(3,3,3-trifluoropropyl)imidazolidin-4-one as a white solid

Sources & evidence

ORD record
ord-79e914e2f4fb41f0ba0e88f4f1420719
Source dataset
uspto-grants-2016_09
Patent number
US09447084B2

Reaction notes

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