Diisopropylethylamine → 4-[5-[3,5-bis(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-N-[2-oxo-3-(2,2,2-trifluoroethyl)-1,3-diazinan-1-yl]-2-(trifluoromethyl)benzamide

HRID 63839Notes

Reaction equation

HRID 63839 reaction equation
[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([C:13]2([C:31]([F:34])([F:33])[F:32])[O:17][N:16]=[C:15]([C:18]3[CH:26]=[CH:25][C:21]([C:22](O)=[O:23])=[C:20]([C:27]([F:30])([F:29])[F:28])[CH:19]=3)[CH2:14]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.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.[NH2:70][N:71]1[CH2:76][CH2:75][CH2:74][N:73]([CH2:77][C:78]([F:81])([F:80])[F:79])[C:72]1=[O:82]>O.CN(C)C=O>[F:36][C:2]([F:1])([F:35])[C:3]1[CH:4]=[C:5]([C:13]2([C:31]([F:32])([F:33])[F:34])[O:17][N:16]=[C:15]([C:18]3[CH:26]=[CH:25][C:21]([C:22]([NH:70][N:71]4[CH2:76][CH2:75][CH2:74][N:73]([CH2:77][C:78]([F:79])([F:81])[F:80])[C:72]4=[O:82])=[O:23])=[C:20]([C:27]([F:28])([F:29])[F:30])[CH:19]=3)[CH2:14]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

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 1180467991-Amino-3-(2,2,2-trifluoroethyl)-1,3-diazinan-2-oneHCID 118046821HCID 118046821, compound

Product 1

HCID 1180466894-[5-[3,5-bis(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-N-[2-oxo-3-(2,2,2-trifluoroethyl)-1,3-diazinan-1-yl]-2-(trifluoromethyl)benzamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Into a 25-mL round-bottom flask, was placed 4-[5-[3,5-bis(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)benzoic acid (100 mg, 0.19 mmol, 1.00 equiv), N,N-dimethylformamide (5 mL), HATU (141 mg, 0.37 mmol, 2.00 equiv), DIEA (96 mg, 0.74 mmol, 4.00 equiv), 1-amino-3-(2,2,2-trifluoroethyl)-1,3-diazinan-2-one (40 mg, 0.20 mmol, 1.10 equiv). The resulting solution was stirred for 3 h at room temperature. The resulting solution was diluted with 20 mL of water. The resulting solution was extracted with 3×20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1×20 mL of brine. The mixture was dried over anhydrous sodium sulfate. The residue was purified by preparative TLC (EtOAc/ether=1:2). This resulted in 34.3 mg (26%) of 4-[5-[3,5-bis(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-N-[2-oxo-3-(2,2,2-trifluoroethyl)-1,3-diazinan-1-yl]-2-(trifluoromethyl)benzamide as a white solid; (ES, m/z): [M+H]+ 719.00, 1H NMR (300 MHz, DMSO): δ 10.72 (s, 1H), 8.37 (s, 1H), 8.23 (s, 2H), 8.16-8.14 (d, J=6 Hz, 1H), 8.08 (s, 1H), 7.74-7.72 (d, 1H), 4.70-4.49 (dd, J=21 Hz, J=45 Hz, 2H), 4.17-4.11 (q, J=9 Hz, 2H), 3.58-3.54 (t, J=6 Hz, 2H), 3.48-3.45 (t, J=5.1 Hz), 2.07-2.05 (m, 2H).

Workup

  1. customInto a 25-mL round-bottom flask, was placed
  2. extractionThe resulting solution was extracted with 3×20 mL of ethyl acetate
  3. washThe resulting mixture was washed with 1×20 mL of brine
  4. dry with materialThe mixture was dried over anhydrous sodium sulfate
  5. customThe residue was purified by preparative TLC (EtOAc/ether=1:2)
  6. customThis resulted in 34.3 mg (26%) of 4-[5-[3,5-bis(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-N-[2-oxo-3-(2,2,2-trifluoroethyl)-1,3-diazinan-1-yl]-2-(trifluoromethyl)benzamide as a white solid

Sources & evidence

ORD record
ord-d68d2c2528d9433e94535c199255b536
Source dataset
uspto-grants-2016_09
Patent number
US09447084B2

Reaction notes

Loading…