Hydrochloric Acid → N1-(4-(2-(6-(3-(Dimethylamino)propoxy)pyridin-3-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N3-(2-methoxyphenyl)malonamide

HRID 2193784Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2193784
[CH3:1][N:2]([CH3:31])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[N:12]=[CH:11][C:10]([C:13]2[S:21][C:20]3[C:15](=[N:16][CH:17]=[CH:18][C:19]=3[O:22][C:23]3[CH:28]=[CH:27][C:26]([NH2:29])=[CH:25][C:24]=3[F:30])[CH:14]=2)=[CH:9][CH:8]=1.CCN(C(C)C)C(C)C.[CH3:41][O:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=1[NH:49][C:50](=[O:55])[CH2:51][C:52](O)=[O:53].C1C=CC2N(O)N=NC=2C=1.Cl>CN(C=O)C.C(Cl)CCl>[CH3:31][N:2]([CH3:1])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[N:12]=[CH:11][C:10]([C:13]2[S:21][C:20]3[C:15](=[N:16][CH:17]=[CH:18][C:19]=3[O:22][C:23]3[CH:28]=[CH:27][C:26]([NH:29][C:52](=[O:53])[CH2:51][C:50]([NH:49][C:44]4[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=4[O:42][CH3:41])=[O:55])=[CH:25][C:24]=3[F:30])[CH:14]=2)=[CH:9][CH:8]=1

Komponenten

8

Edukt 5

HCID 313Hydrochloric Acid2×HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 12664594N-(2-Methoxy-phenyl)-malonamic acidHCID 587900524-(2-(6-(3-(Dimethylamino)propoxy)pyridin-3-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorobenzenamine

Produkt 1

HCID 58790091N1-(4-(2-(6-(3-(Dimethylamino)propoxy)pyridin-3-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N3-(2-methoxyphenyl)malonamideAusbeute 33,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittel2×HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of aniline 380 (0.31 g, 0.71 mmol) and DIPEA (0.7 ml, 0.4 g, 3 mmol) in dry DMF (5 mL) was added acid 27 (0.30 g, 1.4 mmol), HOBt (0.040 g, 0.30 mmol), and EDC×HCl (0.40 g, 2.1 mmol) and the mixture was stirred at r.t. for 18 h. Additional EDC×HCl (0.050 g, 0.26 mmol) was added, and the mixture was stirred for a further 6 h. It was then partitioned between ethyl acetate and water. The organic phase was collected, washed with water, dried (anhydrous MgSO4), filtered, and concentrated. Flash chromatography (chloroform/NH4OH) of the residue followed by re-crystallization (90% ethyl acetate/methanol) provided 378 (0.15 g, 32% yield) as a colorless solid. 1H NMR (400 MHz. DMSO-d6) δ (ppm): 10.58 (br s, 1H); 9.63 (br s, 1H); 8.68 (dd, J=2.7, 0.8, 1H); 8.48 (d, J=5.5, 1H); 8.20 (dd, J=8.6, 2.7, 1H); 8.05 (d, J=7.6, 1H); 8.03 (s, 1H); 7.86 (dd, J=13.1, 2.3, 1H); 7.49 (t, J=8.8, 1H); 7.42 (dd, J=8.8, 1.4, 1H); 7.09-7.03 (m, 2H); 6.94 (dd, J=8.8, 0.7, 1H); 6.92-6.88 (m, 1H); 6.61 (dd, J=5.5, 1.0, 1H); 4.33 (t, J=6.7, 2H); 3.85 (s, 3H); 3.63 (s, 2H); 2.33 (t, J=7.2, 2H); 2.13 (s, 6H); 1.84 (quint, J=7.2, 2H). LRMS (M+H): 630.2.

Aufarbeitung

  1. stirringthe mixture was stirred for a further 6 h
  2. customIt was then partitioned between ethyl acetate and water
  3. customThe organic phase was collected
  4. washwashed with water
  5. dry with materialdried (anhydrous MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customFlash chromatography (chloroform/NH4OH) of the residue followed by re-crystallization (90% ethyl acetate/methanol)

Quellen und Nachweise

ORD-Eintrag
ord-1eccea4b0d96494d9a674c210501b20e
Quelldatensatz
uspto-grants-2012_12
Patentnummer
US08329726B2

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