Dimethylformamide → 4-amino-N-(2-(dimethylamino)ethyl)-3-(3-methoxy-4-(1-methyl-1H-indole-2-carboxamido)phenyl)thieno[3,2-c]pyridine-7-carboxamide

HRID 17182

Reaktionsgleichung

Reaktionsgleichung von HRID 17182
[NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)=[CH:9][S:10][C:6]=2[C:5]([C:32]([OH:34])=O)=[CH:4][N:3]=1.[CH2:35]([N:37]([CH2:40]C)[CH2:38]C)[CH3:36].C[N:43](C)C=O>>[NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)=[CH:9][S:10][C:6]=2[C:5]([C:32]([NH:43][CH2:36][CH2:35][N:37]([CH3:40])[CH3:38])=[O:34])=[CH:4][N:3]=1

Komponenten

4

Edukt 3

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 184508304-amino-3-(3-methoxy-4-(1-methyl-1H-indole-2-carboxamido)phenyl)thieno[3,2-c]pyridine-7-carboxylic acid

Produkt 1

HCID 184508434-amino-N-(2-(dimethylamino)ethyl)-3-(3-methoxy-4-(1-methyl-1H-indole-2-carboxamido)phenyl)thieno[3,2-c]pyridine-7-carboxamideAusbeute 36 %

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

In a 3-necked round bottom flask were combined 4-amino-3-(3-methoxy-4-{[(1-methyl-1H-indol-2-yl)carbonyl]amino}phenyl)thieno[3,2-c]pyridine-7-carboxylic acid (0.100 g, 0.180 mmol) and trans-dichloro[bis(triphenylphosphine)]palladium (II) (0.012 g, 0.018 mmol). The flask was filled and evacuated with nitrogen gas 4 times, followed by the addition of N,N-dimethylformamide (2.5 mL), triethylamine (0.050 mL, 0.361 mmol), and the appropriate amine (0.032 mg, 0.361 mmol). The flask was then filled and evacuated with carbon monoxide gas 3 times and the reaction mixture heated to 90° C. under an atmosphere of carbon monoxide for 4 hours. The reaction was cooled to room temperature, diluted with methylene chloride (50 mL), and washed with water and brine (50 mL each). The organic layer was separated and dried over magnesium sulfate, filtered, and the solvents removed. The crude product was purified by trituration with ethanol to give the title compound (0.034 mg, 36%) as a tan powder. LCMS (Conditions a): Rt 3.00 minutes, 543.3 (MH+); 1H NMR DMSO-d6 δ 9.50 (s, 1 H), 8.54 (s, 1 H), 8.43 (t, J=5.9 Hz, 1 H), 8.00 (d, J=8.2 Hz, 1 H), 7.70 (d, J=7.8 Hz, 1 H), 7.59 (d, J=8.6 Hz, 1 H), 7.58 (s, 1 H), 7.35 (s, 1 H), 7.32 (d, J=8.6 Hz, 1 H), 7.19 (s, 1 H), 7.15 (t, J=7.0 Hz, 1 H), 7.06 (d, J=7.0 Hz, 1 H), 4.04 (s, 3 H), 3.91 (s, 3 H), 3.40 (m, 2 H), 2.43 (m, 2 H), 2.20 (s, 6 H).

Aufarbeitung

  1. customIn a 3-necked round bottom flask were combined
  2. additionThe flask was filled
  3. customevacuated with nitrogen gas 4 times
  4. additionThe flask was then filled
  5. customevacuated with carbon monoxide gas 3 times
  6. temperatureThe reaction was cooled to room temperature
  7. additiondiluted with methylene chloride (50 mL)
  8. washwashed with water and brine (50 mL each)
  9. customThe organic layer was separated
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. customthe solvents removed
  13. customThe crude product was purified by trituration with ethanol

Quellen und Nachweise

ORD-Eintrag
ord-be829b9e6c304f49a5b83c2f44def31a
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07737160B2

Verknüpfte Notizen

Wird geladen…