1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 5-Amino-1-(5-cyclopropylcarbamoyl-2-methyl-phenyl)-3-methyl-1h-pyrazole-4-carboxylic acid ethyl ester

HRID 2041058

Reaktionsgleichung

Reaktionsgleichung von HRID 2041058
[CH2:1]([O:3][C:4]([C:6]1[C:7]([CH3:22])=[N:8][N:9]([C:12]2[CH:17]=[C:16]([C:18]([OH:20])=O)[CH:15]=[CH:14][C:13]=2[CH3:21])[C:10]=1[NH2:11])=[O:5])[CH3:2].CCN=C=N[CH2:28][CH2:29][CH2:30][N:31](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.O>[CH2:1]([O:3][C:4]([C:6]1[C:7]([CH3:22])=[N:8][N:9]([C:12]2[CH:17]=[C:16]([C:18](=[O:20])[NH:31][CH:30]3[CH2:28][CH2:29]3)[CH:15]=[CH:14][C:13]=2[CH3:21])[C:10]=1[NH2:11])=[O:5])[CH3:2]

Komponenten

9

Edukt 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 69828CyclopropylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 670242365-Amino-1-(5-carboxy-2-methyl-phenyl)-3-methyl-1H-pyrazole-4-carboxylic acid ethyl ester

Produkt 1

HCID 112215565-Amino-1-(5-cyclopropylcarbamoyl-2-methyl-phenyl)-3-methyl-1h-pyrazole-4-carboxylic acid ethyl esterAusbeute 17,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of 5-amino-1-(5-carboxy-2-methyl-phenyl)-3-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (150 mg, 0.49 mmol, 1.0 eq), EDCI (190 mg, 0.98 mmol, 2.0 eq), HOBt (134 mg, 0.98 mmol, 2.0 eq), and diisopropylethyl amine (362 μL, 0.98 mmol, 2.0 eq) in DMF (5 mL) which had been stirred at RT for 15 min was added cyclopropylamine (68 μL, 0.98 mmol, 2.0 eq). After stirring overnight, the solution was diluted with EtOAc and water and the organic layer was washed with water (2×) and brine, dried (Na2SO4) and concentrated. The crude residue was purified by flash chromatography on silica gel (gradient elution, 3/2 EtOAc/hexanes then 100% EtOAc) to provide the product as a white solid (29 mg, 17%). HPLC (4 minute 10-95 gradient) tR 1.97 min; MS m/z 343 [M+H]+; 1H NMR (CD3OD), δ 7.87 (d, J=7.1 Hz, 1H), 7.76 (s, 1H), 7.50 (d, J=8.0 Hz, 1H), 4.29 (q, J=7.0 Hz, 2H), 2.84 (m, 1H), 2.34 (s, 3H), 2.18 (s, 3H), 1.36 (t, J=7.0 Hz, 3H), 0.79 (d, J=5.5 Hz, 2H), 0.62 (s, 2H) ppm; 13C NMR (CD3OD), δ 168.1, 164.4, 151.3, 149.8, 140.1, 135.2, 132.6, 130.7, 127.9, 126.3, 92.0, 58.6, 22.1, 15.7, 12.9, 12.6, 4.6 ppm.

Aufarbeitung

  1. washthe organic layer was washed with water (2×) and brine
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customThe crude residue was purified by flash chromatography on silica gel (
  5. washgradient elution, 3/2 EtOAc/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-d66e69d368234576bbb196eaf4554e4e
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08580838B2

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