1,2-Dichloroethane → (Z)-N1-(4-(2-(4-(Dimethylamino)but-1-enyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N3-methyl-N3-phenylmalonamide

HRID 2193737Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2193737
[CH3:1][N:2]([CH3:25])[CH2:3][CH2:4]/[CH:5]=[CH:6]\[C:7]1[S:15][C:14]2[C:9](=[N:10][CH:11]=[CH:12][C:13]=2[O:16][C:17]2[CH:23]=[CH:22][C:20]([NH2:21])=[CH:19][C:18]=2[F:24])[CH:8]=1.[CH3:26][N:27]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:28](=[O:33])[CH2:29][C:30](O)=[O:31].C(Cl)CCl>CN(C=O)C.CCOC(C)=O>[CH3:25][N:2]([CH3:1])[CH2:3][CH2:4]/[CH:5]=[CH:6]\[C:7]1[S:15][C:14]2[C:9](=[N:10][CH:11]=[CH:12][C:13]=2[O:16][C:17]2[CH:23]=[CH:22][C:20]([NH:21][C:30](=[O:31])[CH2:29][C:28]([N:27]([CH3:26])[C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)=[O:33])=[CH:19][C:18]=2[F:24])[CH:8]=1

Komponenten

6

Edukt 3

HCID 111,2-Dichloroethane2×HCID 3500563-(Methyl(phenyl)amino)-3-oxopropanoic acid2×HCID 58790344(Z)-4-(2-(4-(Dimethylamino)but-1-enyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluoroaniline

Produkt 1

HCID 58790146(Z)-N1-(4-(2-(4-(Dimethylamino)but-1-enyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N3-methyl-N3-phenylmalonamideAusbeute 34,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A solution of (Z)-4-(2-(4-(dimethylamino)but-1-enyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluoroaniline (235) (69.1 mg, 0.193 mmol), 3-(methyl(phenyl)amino)-3-oxopropanoic acid 31 (46 mg, 0.26 mmol) (scheme 10), and EDC (45 mg, 0.24 mmol) in DMF (2.8 mL) was stirred overnight at room temperature. More 31 (45 mg, 0.26 mmol) and EDC (45 mg, 0.24 mmol) were added and the mixture stirred 6 h more. The mixture was diluted with EtOAc, washed with water, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was redissolved in MeOH and purified twice by preparative HPLC (gradient 40% to 95% MeOH in water, 45 min) giving title compound 231 (35 mg, 0.066 mmol, 34% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 10.32 (s, 1H), 8.48 (d, J=5.5 Hz, 1H), 7.80 (d, J=12.7 Hz, 1H), 7.54 (s, 1H), 7.5-7.3 (m, 7H), 6.78 (d, J=12.2 Hz, 1H), 6.62 (d, J=5.5 Hz, 1H), 5.92 (tt, J=7.2 Hz, J=4.5 Hz, 11.7 Hz, 1H), 3.21 (s, 5H), 2.59 (m, 2H), 2.42 (dd, 6.8 Hz, 7.4 Hz, 2H), 2.16 (s, 6H). MS (m/z): (M+1) 533.1 (100 N.

Aufarbeitung

  1. washwashed with water
  2. dry with materialdried over anhydrous Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was redissolved in MeOH
  5. custompurified twice by preparative HPLC (gradient 40% to 95% MeOH in water, 45 min)

Quellen und Nachweise

ORD-Eintrag
ord-6b1b9d914ed84e2381c76ade9fba9203
Quelldatensatz
uspto-grants-2012_12
Patentnummer
US08329726B2

Notizen zur Reaktion

Wird geladen…