Triethylamine → HCID 44252754, compound

HRID 19130Notes

Reaction equation

HRID 19130 reaction equation
[CH3:1][CH:2]([CH3:22])[CH2:3][C@H:4]([N:8]1[CH2:12][C:11]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH3:20])=[CH:10][C:9]1=[O:21])[C:5]([OH:7])=O.Cl.[OH:24][C@@H:25]([CH2:55]O)[CH2:26][N:27]1[CH:31]=[CH:30][C:29]([NH:32]C(=O)[C@@H](N2CC(OC3C=CC=C(Cl)C=3Cl)=CC2=O)CC(C)C)=[N:28]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=C[C:67]=2N=N1.C(N(CC)CC)C>CN(C)C=O>[OH:24][C:25]([CH3:55])([CH3:67])[CH2:26][N:27]1[CH:31]=[CH:30][C:29]([NH:32][C:5](=[O:7])[C@@H:4]([N:8]2[CH2:12][C:11]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[CH3:20])=[CH:10][C:9]2=[O:21])[CH2:3][CH:2]([CH3:1])[CH3:22])=[N:28]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 66893909HCID 66893909, compoundHCID 66899094HMS5552 HCl

Product 1

HCID 44252754HCID 44252754, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (S)-4-methyl-2-(2-oxo-4-o-tolyloxy-2,5-dihydro-pyrrol-1-yl)-pentanoic acid (prepared as in Example 120, 0.214 g, 0.71 mmol) in N,N-dimethylformamide (4.5 mL) was added 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 0.142 g, 0.91 mmol) and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (0.618 g, 1.40 mmol). The mixture was stirred at 0° C. and triethylamine (0.142 g, 1.40 mmol) was added. The mixture was stirred at room temperature for 4 h and the solvents were evaporated. The residue was treated with ethyl acetate and ammonium chloride solution, and the organic layer separated. 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 25 g, 30% to 100% ethyl acetate/hexanes) which afforded (S)-4-methyl-2-(2-oxo-4-o-tolyloxy-2,5-dihydro-pyrrol-1-yl)-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide (0.112 g, 36%) as a tan solid: HR-ES-MS m/z calculated for C24H32N4O4 [M+H]+ 441.2497, observed 441.2496, 1H NMR (300 MHz, DMSO-d6) δ ppm 1.00 0.89 (d, J=6.3 Hz, 3H), 0.93 (d, J=6.3 Hz, 3H), 1.04 (br. s., 3H), 1.06 (br. s., 3H), 1.37-1.64 (m, 2H), 1.66-1.85 (m, 1H), 2.19 (s, 3H), 3.89 (br. s., 2H), 4.20 (d, J=18.1 Hz, 1H), 4.59 (d, J=18.1 Hz, 1H), 4.63 (s, 1H), 4.68 (s, 1H), 4.88 (dd, J=10.4, 4.4 Hz, 1H), 6.44 (d, J=2.1 Hz, 1H), 7.11-7.32 (m, 3H), 7.35 (d, J=6.6 Hz, 1H), 7.53 (d, J=2.1 Hz, 1H), 10.79 (br. s., 1H).

Workup

  1. stirringThe mixture was stirred at room temperature for 4 h
  2. customthe solvents were evaporated
  3. additionThe residue was treated with ethyl acetate and ammonium chloride solution
  4. customthe organic layer separated
  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 25 g, 30% to 100% ethyl acetate/hexanes) which

Sources & evidence

ORD record
ord-11cda62588614288b8db80ee075bbb78
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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