Diisopropylethylamine → HCID 44252756, compound

HRID 19136Notes

Reaction equation

HRID 19136 reaction equation
[F:1][C:2]1[C:22]([OH:23])=[CH:21][CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH2:9][N:8]([C@@H:10]([CH2:14][CH:15]([CH3:17])[CH3:16])[C:11]([OH:13])=O)[C:7](=[O:18])[CH:6]=1.[CH3:24][N:25]1[CH:29]=[CH:28][C:27]([NH2:30])=[N:26]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH3:24][N:25]1[CH:29]=[CH:28][C:27]([NH:30][C:11](=[O:13])[C@@H:10]([N:8]2[CH2:9][C:5]([O:4][C:3]3[CH:19]=[CH:20][CH:21]=[C:22]([OH:23])[C:2]=3[F:1])=[CH:6][C:7]2=[O:18])[CH2:14][CH:15]([CH3:17])[CH3:16])=[N:26]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 1372541-Methyl-3-aminopyrazoleHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 66894967(S)-2-[4-(2-fluoro-3-hydroxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid

Product 1

HCID 44252756HCID 44252756, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (S)-2-[4-(2-fluoro-3-hydroxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid (prepared as in Example 126, 0.226 g, 0.70 mmol) in N,N-dimethylformamide (4 mL) was added 1-methyl-1H-pyrazol-3-ylamine (0.340 g, 3.50 mmol) and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (0.340 g, 0.77 mmol). The mixture was stirred at 0° C. and N,N-diisopropylethylamine (0.108 g, 0.84 mmol) was added. The mixture was stirred at room temperature overnight and the solvents were evaporated. The residue was extracted with ethyl acetate and washed with a citric acid solution. The organic layer was washed with brine and dried over sodium sulfate. The solvents were evaporated and the residue was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g, 10% to 100% (9:1 dichloromethane:methanol)/hexanes) which afforded (S)-2-[4-(2-fluoro-3-hydroxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid (1-methyl-1H-pyrazol-3-yl)-amide (0.115 g, 41%) as a white solid: HR-ES-MS m/z calculated for C20H23FN4O4 [M+Na]+ 425.1595, observed 425.1597, 1H NMR (400 MHz, DMSO-d6) δ ppm 1.00 0.90 (d, J=6.4 Hz, 3H), 0.93 (d, J=6.4 Hz, 3H), 1.45 (m, 1H), 1.53-1.63 (m, 1H), 1.67-1.79 (m, 1H), 3.73 (s, 3H), 4.20 (d, J=18.5 Hz, 1H), 4.57 (d, J=18.5 Hz, 1H), 4.84-4.92 (m, 2H), 6.40 (d, J=1.7 Hz, 1H), 6.85 (t, J=7.8 Hz, 1H), 6.91 (t, J=7.8 Hz, 1H), 7.05 (t, J=7.8 Hz, 1H), H), 7.54 (d, J=1.7 Hz, 1H), 10.35 (br. s., 1H), 10.72 (s, 1H).

Workup

  1. stirringThe mixture was stirred at room temperature overnight
  2. customthe solvents were evaporated
  3. extractionThe residue was extracted with ethyl acetate
  4. washwashed with a citric acid solution
  5. washThe organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. customThe solvents were evaporated
  8. customthe residue was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g, 10% to 100% (9:1 dichloromethane:methanol)/hexanes) which

Sources & evidence

ORD record
ord-d0acdc09d66b4b28bb92527dc5c3e3f4
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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