Triethylamine → Ethyl 3-(4-((3,3-dimethylcyclobutyl)(quinolin-3-ylamino)methyl)benzamido)propanoate

HRID 2281144Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2281144
[CH3:1][C:2]1([CH3:27])[CH2:5][CH:4]([CH:6]([NH:16][C:17]2[CH:18]=[N:19][C:20]3[C:25]([CH:26]=2)=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:7]2[CH:15]=[CH:14][C:10]([C:11](O)=[O:12])=[CH:9][CH:8]=2)[CH2:3]1.[CH2:28]([O:30][C:31](=[O:35])[CH2:32][CH2:33][NH2:34])[CH3:29].ON1C2N=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C>C(Cl)Cl>[CH3:27][C:2]1([CH3:1])[CH2:5][CH:4]([CH:6]([NH:16][C:17]2[CH:18]=[N:19][C:20]3[C:21]([CH:26]=2)=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:7]2[CH:15]=[CH:14][C:10]([C:11]([NH:34][CH2:33][CH2:32][C:31]([O:30][CH2:28][CH3:29])=[O:35])=[O:12])=[CH:9][CH:8]=2)[CH2:3]1

Komponenten

7

Edukt 5

HCID 8471TriethylamineHCID 181649HOAtHCID 419889Ethyl 3-aminopropanoateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 712393444-((3,3-Dimethylcyclobutyl)(quinolin-3-ylamino)methyl)benzoic acid

Produkt 1

HCID 71239304Ethyl 3-(4-((3,3-dimethylcyclobutyl)(quinolin-3-ylamino)methyl)benzamido)propanoateAusbeute 66,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a vial containing 4-((3,3-dimethylcyclobutyl)(quinolin-3-ylamino)methyl)benzoic acid (14.0 mg, 0.0390 mmol) was added 3-aminopropionic acid ethyl ester hydrochloric (6.60 mg, 0.0430 mmol), 1-Hydroxy-7-azabenzotriazole (6.40 mg, 0.0470 mmol) and 1-ethyl-3-(3-dimethylamino propyl)carbodiimide hydrochloride (9.00 mg, 0.0470 mmol). Anhydrous methylene chloride (0.390 mL) was added followed by triethylamine (0.007 mL, 0.0510 mmol). After 18 h, the reaction was diluted with methylene chloride and quenched with a saturated solution of ammonium chloride. The aqueous layer was extracted three times with methylene chloride. The combined organic layers were dried with sodium sulfate, filtered, and concentrated to give 26.0 mg of crude material. Purification by column chromatography (0-70% ethyl acetate in heptane) provided ethyl 3-(4-((3,3-dimethylcyclobutyl)(quinolin-3-ylamino)methyl)benzamido)propanoate (11.9 mg, 66% yield) as an oil. 1H NMR (400 MHz, CDCl3) δ: 8.48 (d, J=2.7 Hz, 1H), 7.88 (dd, J=8.3, 1.3 Hz, 1H), 7.74-7.67 (m, 2H), 7.46-7.41 (m, 2H), 7.41-7.29 (m, 3H), 6.81 (t, J=6.1 Hz, 1H), 6.69 (d, J=2.7 Hz, 1H), 4.42 (br. s., 1H), 4.25 (dd, J=9.3, 4.4 Hz, 1H), 4.19-4.08 (m, 2H), 3.70 (q, J=6.0 Hz, 2H), 2.61 (t, J=5.7 Hz, 2H), 2.59-2.45 (m, 1H), 2.07-1.97 (m, 1H), 1.76-1.67 (m, 2H), 1.66-1.55 (m, 1H), 1.28-1.21 (m, 3H), 1.13 (s, 3H), 1.09 (m, 3H). MS (M+1): 460.4.

Aufarbeitung

  1. customquenched with a saturated solution of ammonium chloride
  2. extractionThe aqueous layer was extracted three times with methylene chloride
  3. dry with materialThe combined organic layers were dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give 26.0 mg of crude material
  7. customPurification by column chromatography (0-70% ethyl acetate in heptane)

Quellen und Nachweise

ORD-Eintrag
ord-70c388923bbb42369a5882ded04d546b
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09139538B2

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