Diisopropylethylamine → HCID 57920131, compound

HRID 19403Notes

Reaction equation

HRID 19403 reaction equation
[N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[NH:7][C:8](=[O:15])[C@@H:9]([NH2:14])[CH2:10][CH:11]([CH3:13])[CH3:12].CN1C=CC(NC(=O)[C@@H](N2[CH2:33][C:32]([O:34][C:35]3[CH:40]=[CH:39][CH:38]=[C:37]([CH2:41][C:42]([OH:45])([CH3:44])[CH3:43])[CH:36]=3)=[CH:31][C:30]2=[O:46])CC(C)C)=N1.C(N(CC)C(C)C)(C)C>C(#N)C>[N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[NH:7][C:8](=[O:15])[C@@H:9]([N:14]1[CH2:33][C:32]([O:34][C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([CH2:41][C:42]([OH:45])([CH3:43])[CH3:44])[CH:36]=2)=[CH:31][C:30]1=[O:46])[CH2:10][CH:11]([CH3:12])[CH3:13]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 57920146HCID 57920146, compoundHCID 61154753HCID 61154753, compound

Product 1

HCID 57920131HCID 57920131, compoundYield 22.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (S)-2-amino-4-methyl-pentanoic acid pyrazin-2-ylamide (prepared as in Example 245, 0.400 g, 1.92 mmol), (E)-4-bromo-3-[3-(2-hydroxy-2-methyl-propyl)-phenoxy]-but-2-enoic acid ethyl ester (prepared as in Example 235, 0.462 g, 1.29 mmol) and N,N-diisopropylethylamine (0.734 g, 5.69 mmol) in acetonitrile (16.6 mL) were sealed in a tube and heated at 100° C. for 12 h. The mixture was cooled and concentrated in vacuo. The residue was partitioned between ethyl acetate (20 mL) and water (20 mL) and the phases separated. The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was dissolved in tetrahydrofuran (5 mL), sealed in an Emry Optimizer microwave tube and microwaved at 160° C. for 4 h. The mixture was cooled and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, 5% to 35% ethyl acetate/hexanes) to afford (S)-2-{4-[3-(2-hydroxy-2-methyl-propyl)-phenoxy]-2-oxo-2,5-dihydro-pyrrol-1-yl}-4-methyl-pentanoic acid pyrazin-2-ylamide (127 mg, 22%) as a tan solid: HR-ES-MS m/z calculated for C24H30N4O4 [M+H]+ 439.234, observed 439.2341; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.91 (d, J=6.9 Hz, 3H), 0.93 (d, J=6.9 Hz, 3H), 1.04 (s, 6H), 1.39-1.70 (m, 2H), 1.72-1.87 (m, 1H), 2.66 (s, 2H), 4.21 (d, J=18.4 Hz, 1H), 4.36 (s, 1H), 4.55 (d, J=18.4 Hz, 1H), 4.83 (s, 1H), 5.02 (dd, J=10.9, 4.5 Hz, 1H), 6.94-7.19 (m, 3H), 7.34 (t, J=7.5 Hz, 1H), 8.36 (d, J=2.7 Hz, 1H), 8.41 (d, J=1.5 Hz, 1H), 9.26 (s, 1H), 11.16 (s, 1H).

Workup

  1. customwere sealed in a tube
  2. temperatureThe mixture was cooled
  3. concentrationconcentrated in vacuo
  4. customThe residue was partitioned between ethyl acetate (20 mL) and water (20 mL)
  5. customthe phases separated
  6. dry with materialThe organic phase was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. dissolutionThe residue was dissolved in tetrahydrofuran (5 mL)
  10. customsealed in an Emry Optimizer microwave tube
  11. custommicrowaved at 160° C. for 4 h
  12. temperatureThe mixture was cooled
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified by flash column chromatography (silica gel, 5% to 35% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-8cc5d7f3e82543628db68eb0c429ed92
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

Loading…