1-Hydroxybenzotriazole → N1-(4-(2-(3-((Dimethylamino)methyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N3-(2-methoxyphenyl)malonamide

HRID 418653

Reaktionsgleichung

Reaktionsgleichung von HRID 418653
[CH3:1][N:2]([CH2:4][C:5]1[CH:6]=[C:7]([C:11]2[S:19][C:18]3[C:13](=[N:14][CH:15]=[CH:16][C:17]=3[O:20][C:21]3[CH:27]=[CH:26][C:24]([NH2:25])=[CH:23][C:22]=3[F:28])[CH:12]=2)[CH:8]=[CH:9][CH:10]=1)[CH3:3].[CH3:29][O:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[NH:37][C:38](=[O:43])[CH2:39][C:40](O)=[O:41].ON1C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C.Cl>CN(C)C=O>[CH3:3][N:2]([CH2:4][C:5]1[CH:6]=[C:7]([C:11]2[S:19][C:18]3[C:13](=[N:14][CH:15]=[CH:16][C:17]=3[O:20][C:21]3[CH:27]=[CH:26][C:24]([NH:25][C:40](=[O:41])[CH2:39][C:38]([NH:37][C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=4[O:30][CH3:29])=[O:43])=[CH:23][C:22]=3[F:28])[CH:12]=2)[CH:8]=[CH:9][CH:10]=1)[CH3:1]

Komponenten

6

Edukt 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 12664594N-(2-Methoxy-phenyl)-malonamic acidHCID 587901024-(2-(3-((Dimethylamino)methyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluoroaniline

Produkt 1

HCID 16042361N1-(4-(2-(3-((Dimethylamino)methyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N3-(2-methoxyphenyl)malonamideAusbeute 36,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of the amine 150 (334 mg, 0.85 mmol), 3-(2-methoxyphenylamino)-3-oxopropanoic acid (27) (355 mg, 1.70 mmol), 1-hydroxybenzotriazole (275 mg, 2.04 mmol) in dimethylformamide (8.5 mL) was added N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (391 mg, 2.04 mmol) and the reaction mixture was stirred at room temperature until completion of the reaction. The dimethylformamide was evaporated and the residue was quenched with a saturated solution of sodium bicarbonate. The aqueous layer was extracted three times with ethyl acetate. The combined organic layers were washed with water and brine, dried over anhydrous MgSO4, filtered and evaporated to afford title compound 146 as a white solid (180 mg, 36% yield). 1H NMR (DMSO-d6) 6 (Ppm): 10.59 (s, 1H), 9.64 (s, 1H), 8.52-8.50 (m, 1H), 8.08-8.06 (m, 2H), 7.88 (d, J=12.9 Hz, 1H), 7.78 (m, 2H), 7.51-7.38 (m, 4H), 7.07 (s, 2H), 6.92 (m, 1H), 6.65 (m, 1H), 3.86 (s, 3H), 3.65 (s, 2H), 3.48 (s, 2H), 2.18 (s, 6H). MS (m/z): 585.2 (M+H).

Aufarbeitung

  1. customThe dimethylformamide was evaporated
  2. customthe residue was quenched with a saturated solution of sodium bicarbonate
  3. extractionThe aqueous layer was extracted three times with ethyl acetate
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-2640522338604c32b624ecd90d1bc515
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08093264B2

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