Diisopropylethylamine → HCID 57920146, compound

HRID 19375Notes

Reaction equation

HRID 19375 reaction equation
[OH:1][C:2]([CH3:26])([CH3:25])[CH2:3][C:4]1[CH:5]=[C:6]([CH:22]=[CH:23][CH:24]=1)[O:7][C:8]1[CH2:12][N:11]([C@@H:13]([CH2:17][CH:18]([CH3:20])[CH3:19])[C:14]([OH:16])=O)[C:10](=[O:21])[CH:9]=1.[CH3:27][N:28]1[CH:32]=[CH:31][C:30]([NH2:33])=[N:29]1.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>ClCCl.O.C(OCC)(=O)C>[CH3:27][N:28]1[CH:32]=[CH:31][C:30]([NH:33][C:14](=[O:16])[C@@H:13]([N:11]2[CH2:12][C:8]([O:7][C:6]3[CH:22]=[CH:23][CH:24]=[C:4]([CH2:3][C:2]([OH:1])([CH3:26])[CH3:25])[CH:5]=3)=[CH:9][C:10]2=[O:21])[CH2:17][CH:18]([CH3:19])[CH3:20])=[N:29]1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 1372541-Methyl-3-aminopyrazoleHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 66895240HCID 66895240, compound

Product 1

HCID 57920146HCID 57920146, compoundYield 62%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-2-{4-[3-(2-hydroxy-2-methyl-propyl)-phenoxy]-2-oxo-2,5-dihydro-pyrrol-1-yl}-4-methyl-pentanoic acid (0.100 g, 0.28 mmol) in dichloromethane (10 mL) was added 1-methyl-1H-pyrazol-3-ylamine (0.040 g, 0.41 mmol), N,N-diisopropylethylamine (0.110 g, 0.85 mmol) and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (0.180 g, 0.41 mmol) at 0° C. The mixture was allowed to slowly warm up to room temperature and then stirred for 2 h. The mixture was partioned between ethyl acetate and water. The organic layer was then collected and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel 30% to 100% ethyl acetate/hexanes) which afforded (S)-2-{4-[3-(2-hydroxy-2-methyl-propyl)-phenoxy]-2-oxo-2,5-dihydro-pyrrol-1-yl}-4-methyl-pentanoic acid (1-methyl-1H-pyrazol-3-yl)-amide (0.075 g, 62%) as a white solid: HR-ES-MS m/z calculated for C24H32N4O4 [M+H]+ 441.2497, observed 441.2497; 1H NMR (300 MHz, CDCl3) δ ppm 0.92-1.01 (m, 6H), 1.24 (s, 6H), 1.40-1.69 (m, 2H), 1.68-1.97 (m, 2H), 2.78 (s, 2H), 3.82 (br. s., 3H), 4.07 (d, J=18.1 Hz, 1H), 4.27 (d, J=17.5 Hz, 1H), 4.79-4.94 (m, 1H), 4.97 (s, 1H), 6.60 (br. s., 1H), 7.07 (br. s., 2H), 7.14 (d, J=7.5 Hz, 1H), 7.30-7.40 (m, 2H), 8.55 (br. s., 1H).

Workup

  1. customThe organic layer was then collected
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by flash column chromatography (silica gel 30% to 100% ethyl acetate/hexanes) which

Sources & evidence

ORD record
ord-c198adec96314f5bac39df96a4f3a42c
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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