1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 3-(5-amino-4-benzoyl-pyrazol-1-yl)-N-cyclopropyl-4-methylbenzamide

HRID 2041028Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2041028
[NH2:1][C:2]1[N:6]([C:7]2[CH:8]=[C:9]([CH:13]=[CH:14][C:15]=2[CH3:16])[C:10](O)=[O:11])[N:5]=[CH:4][C:3]=1[C:17](=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.CCN=C=N[CH2:30][CH2:31][CH2:32][N:33](C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.C1(N)CC1>CN(C=O)C.CCOC(C)=O>[NH2:1][C:2]1[N:6]([C:7]2[CH:8]=[C:9]([CH:13]=[CH:14][C:15]=2[CH3:16])[C:10]([NH:33][CH:32]2[CH2:30][CH2:31]2)=[O:11])[N:5]=[CH:4][C:3]=1[C:17](=[O:24])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Komponenten

8

Edukt 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 69828CyclopropylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 112094383-(5-amino-4-benzoyl-1H-pyrazol-1-yl)-4-methylbenzoic acid

Produkt 1

HCID 114852003-(5-amino-4-benzoyl-pyrazol-1-yl)-N-cyclopropyl-4-methylbenzamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a stirred solution of 3-(5-amino-4-benzoyl-pyrazol-1-yl)-4-methyl-benzoic acid 5 (Example 3, 700 mg, 2.18 mmol, 1.0 eq) in 30 mL of DMF was added EDCI (855 mg 4.35 mmol, 2.0 eq), HOBt (589 mg, 4.35 mmol, 2.0 eq), and diisopropylethylamine (1.59 mL, 8.71 mmol, 4.0 eq) and the solution was stirred for 15 minutes at room temperature when cyclopropylamine (302 μL, 4.35 mmol, 2.0 eq) was added and the reaction stirred for 1 hour. The mixture was diluted with EtOAc (300 mL) and washed with water (2×25 mL) and brine (25 mL), dried (Na2SO4) and concentrated. The product was purified by flash chromatography on silica gel eluted with 8/2 EtOAc/MeOH to provide the product as a brown oil. The product was further purified by trituration with 1/1/1 EtOAc/hexanes/CH2Cl2 and dried under vacuum to provide 3-(5-amino-4-benzoyl-pyrazol-1-yl)-N-cyclopropyl-4-methyl-benzamide 6 (387 mg, 50%) as a white powder: HPLC (4 minute gradient) tR 2.11 min; MS m/z 361 [M+H]; 1H NMR (CD3OD, 300 MHz) δ 7.92 (d, J=7.6, 1H), 7.81 (m, 4H), 7.54 (m, 4H), 2.85 (m, 1H), 2.22 (s, 3H), 0.80 (d, J=5.7, 2 H), 0.63 (s, 2H) ppm; 13C NMR (CD3OD, 75 MHz) δ 191.2, 170.1, 153.8, 143.3, 142.0, 141.1, 136.9, 134.8, 132.9, 132.7, 130.1, 129.7, 129.2, 128.1, 104.8, 24.1, 17.7, 6.6 ppm.

Aufarbeitung

  1. additionwas added
  2. washwashed with water (2×25 mL) and brine (25 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe product was purified by flash chromatography on silica gel
  6. washeluted with 8/2 EtOAc/MeOH

Quellen und Nachweise

ORD-Eintrag
ord-63f42c0222424647b37f316ef2bb1c52
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08580838B2

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