1-Hydroxybenzotriazole → (S)-3-cyclohexyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-(2-oxo-4-phenoxy-2,5-dihydro-pyrrol-1-yl)-propionamide

HRID 19298Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 19298
[CH:1]1([CH2:7][C@H:8]([N:12]2[CH2:16][C:15]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:14][C:13]2=[O:24])[C:9]([OH:11])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[CH3:26]N(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.ON1C2C=CC=CC=2N=N1.Cl.[OH:57][C@@H:58]([CH2:88]O)[CH2:59][N:60]1[CH:64]=[CH:63][C:62]([NH:65]C(=O)[C@@H](N2CC(OC3C=CC=C(Cl)C=3Cl)=CC2=O)CC(C)C)=[N:61]1>ClCCl.C(OCC)(=O)C>[CH:1]1([CH2:7][C@H:8]([N:12]2[CH2:16][C:15]([O:17][C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)=[CH:14][C:13]2=[O:24])[C:9]([NH:65][C:62]2[CH:63]=[CH:64][N:60]([CH2:59][C:58]([OH:57])([CH3:88])[CH3:26])[N:61]=2)=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Komponenten

8

Edukt 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66895449(S)-3-cyclohexyl-2-(2-oxo-4-phenoxy-2,5-dihydro-pyrrol-1-yl)-propionic acidHCID 66899094HMS5552 HCl

Produkt 1

HCID 57920090(S)-3-cyclohexyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-(2-oxo-4-phenoxy-2,5-dihydro-pyrrol-1-yl)-propionamideAusbeute 22,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
23 °C

Versuchsvorschrift

To a stirred solution of (S)-3-cyclohexyl-2-(2-oxo-4-phenoxy-2,5-dihydro-pyrrol-1-yl)-propionic acid (80 mg, 0.2 mmol) in dichloromethane (8 mL) was gradually added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (137 mg, 0.7 mmol) and N,N-diisopropylethylamine (155 mg, 1.2 mmol) at room temperature, under nitrogen. After 15 min, 1-hydroxybenzotriazole (110 mg, 0.7 mmol) and 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 37 mg, 0.2 mmol) were added to the reaction mixture. The reaction mixture was then stirred at 23° C. for 48 h. The reaction mixture was diluted with ethyl acetate and washed with a saturated aqueous ammonium chloride solution followed by a saturated aqueous sodium bicarbonate solution. The organic layer was then washed with a saturated aqueous sodium chloride solution, separated, dried over sodium sulfate and concentrated in vacuo to afford the crude product, which was purified by flash column chromatography (silica gel (100-200 mesh)) which afforded (S)-3-cyclohexyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-(2-oxo-4-phenoxy-2,5-dihydro-pyrrol-1-yl)-propionamide (21 mg, 19%) as an off-white gummy solid: 1H NMR (400 MHz, CDCl3) δ ppm 0.83-1.08 (m, 2H), 1.13 (s, 6H), 1.24 (s, 3H), 1.58-2.06 (m, 8H), 3.77 (br. s., 1H), 3.91 (s, 2H), 4.08 (d, J=18.1 Hz, 1H), 4.32 (d, J=18.1 Hz, 1H), 4.87-4.96 (m, 1H), 4.96 (s, 1H), 6.67 (s, 1H), 7.15 (d, J=7.8 Hz, 2H), 7.20-7.31 (m, 1H), 7.39 (t, J=7.8 Hz, 2H), 9.01 (s, 1H).

Aufarbeitung

  1. customat room temperature
  2. washwashed with a saturated aqueous ammonium chloride solution
  3. washThe organic layer was then washed with a saturated aqueous sodium chloride solution
  4. customseparated
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customto afford the crude product, which
  8. customwas purified by flash column chromatography (silica gel (100-200 mesh)) which

Quellen und Nachweise

ORD-Eintrag
ord-81fe88e143b14319b9329575cc39cdeb
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07741327B2

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