Pyridine → N-isoxazol-3-yl-4-methyl-3-[1-oxo-7-(2-piperidin-1-ylethoxy)isoquinolin-2(1H)-yl]benzamide

HRID 506987

Reaktionsgleichung

Reaktionsgleichung von HRID 506987
[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[CH:4][C:3]=1[N:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][N:24]3[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]3)=[CH:16][CH:17]=2)[C:12]1=[O:30].C(Cl)(=O)C(Cl)=O.N1C=CC=CC=1.[NH2:43][C:44]1[CH:48]=[CH:47][O:46][N:45]=1>C(Cl)Cl.CN(C=O)C.C(OCC)(=O)C>[O:46]1[CH:47]=[CH:48][C:44]([NH:43][C:6](=[O:7])[C:5]2[CH:9]=[CH:10][C:2]([CH3:1])=[C:3]([N:11]3[CH:20]=[CH:19][C:18]4[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][N:24]5[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]5)=[CH:16][CH:17]=4)[C:12]3=[O:30])[CH:4]=2)=[N:45]1

Komponenten

8

Edukt 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 18102163-IsoxazolamineHCID 670185784-Methyl-3-[1-oxo-7-(2-piperidin-1-ylethoxy)isoquinolin-2(1H)-yl]benzoic acid

Produkt 1

HCID 67018575N-isoxazol-3-yl-4-methyl-3-[1-oxo-7-(2-piperidin-1-ylethoxy)isoquinolin-2(1H)-yl]benzamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

4-Methyl-3-[1-oxo-7-(2-piperidin-1-ylethoxy)isoquinolin-2(1H)-yl]benzoic acid (439 mg) was dissolved in methylene chloride (5 ml) and DMF (3 drops) and cooled to 0° C. under an argon atmosphere. Oxalyl chloride (0.19 ml) was added and the reaction mixture stirred at room temperature for 2 hours. Pyridine (0.90 ml) and 3-aminoisoxazole (0.40 ml) were added and the reaction mixture stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate, washed with 1N NaOH, dried (magnesium sulfate) and concentrated. Purification by column chromatography on an ion exchange column (isolute SCX column from International Sorbent Technology Limited, Henoed, Mid-Glamorgan, UK) using initially methanol and then a 99:1 mixture of methanol and aqueous ammonia solution to give a solid. The solid was triturated with ethyl acetate to give N-isoxazol-3-yl-4-methyl-3-[1-oxo-7-(2-piperidin-1-ylethoxy)isoquinolin-2(1H)-yl]benzamide as a solid (95 mg); NMR Spectrum: (DMSOd6) 1.40 (m, 2H), 1.45 (m, 4H), 2.15 (s, 3H), 2.49 (m, 4H), 2.70 (m, 2H), 4.15 (m, 2H), 6.75 (d, 1H), 7.05 (d, 1H), 7.25 (d, 1H), 7.43 (d, 1H), 7.60 (d, 1H), 7.68 (d, 1H), 7.73 (d, 1H), 8.00 (s, 1H), 8.05 (d, 1H), 8.85 (s, 1H), 11.50 (s, 1H); Mass Spectrum: M+H+ 473.

Aufarbeitung

  1. stirringthe reaction mixture stirred at room temperature for 2 hours
  2. washwashed with 1N NaOH
  3. dry with materialdried (magnesium sulfate)
  4. concentrationconcentrated
  5. customPurification by column chromatography on an ion exchange column (isolute SCX column from International Sorbent Technology Limited, Henoed, Mid-Glamorgan, UK)
  6. additiona 99:1 mixture of methanol and aqueous ammonia solution
  7. customto give a solid
  8. customThe solid was triturated with ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-529599ea4c77418790db86d53f8e32f3
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07786115B2

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