Hydrochloric Acid → 5-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-8,10-difluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2',3':4,5]pyrimido[6,1-b]quinazolin-7(3H)-one

HRID 1014480

Reaktionsgleichung

Reaktionsgleichung von HRID 1014480
Cl[C:2]1[N:3]=[C:4]([NH:21][C:22]2[CH:30]=[C:29]([F:31])[CH:28]=[C:27]([F:32])[C:23]=2[C:24]([NH2:26])=[O:25])[C:5]2[CH:10]=[CH:9][N:8]([S:11]([C:14]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:6]=2[N:7]=1.[CH3:33][N:34]([CH2:36][C:37]([N:39]1[C:47]2[C:42](=[CH:43][C:44]([O:49][CH3:50])=[C:45](N)[CH:46]=2)[CH2:41][CH2:40]1)=[O:38])[CH3:35].Cl.[I-].[K+]>FC(F)(F)CO.O1CCOCC1.ClCCl.C(=O)(O)[O-].[Na+]>[CH3:33][N:34]([CH3:35])[CH2:36][C:37]([N:39]1[C:47]2[C:42](=[CH:43][C:44]([O:49][CH3:50])=[C:45]([NH:3][C:2]3[N:26]4[C:4](=[N:21][C:22]5[C:23]([C:24]4=[O:25])=[C:27]([F:32])[CH:28]=[C:29]([F:31])[CH:30]=5)[C:5]4[CH:10]=[CH:9][N:8]([S:11]([C:14]5[CH:15]=[CH:16][C:17]([CH3:20])=[CH:18][CH:19]=5)(=[O:13])=[O:12])[C:6]=4[N:7]=3)[CH:46]=2)[CH2:41][CH2:40]1)=[O:38]

Komponenten

9

Edukt 4

HCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 534147641-(6-Amino-5-methoxy-2,3-dihydro-1H-indol-1-yl)-2-(dimethylamino)ethan-1-oneHCID 86644196HCID 86644196, Verbindung

Produkt 1

HCID 673166665-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-8,10-difluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2',3':4,5]pyrimido[6,1-b]quinazolin-7(3H)-oneAusbeute 95,1 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 6344DichloromethaneLösungsmittelHCID 64092,2,2-TrifluoroethanolLösungsmittelHCID 312751,4-DioxaneLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

To a suspension of 2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-4,6-difluorobenzamide (1.96 g, 4.1 mmol) in 2,2,2-trifluoroethanol (40 mL) was added 1-[(dimethylamino)acetyl]-5-(methyloxy)-2,3-dihydro-1H-indol-6-amine (1.33 g, 5.33 mmol), hydrochloric acid as a 4.0M solution in dioxane (4.1 mL), and catalytic potassium iodide (<10 mg). The resulting slurry was stirred at 90° C. in a pressure vial for 40 hours, at which time all solids had completely dissolved. The resulting solution was cooled to room temperature and diluted with dichloromethane and saturated sodium bicarbonate as to adjust the aqueous layer to pH>10. The organic layer was washed with water and saturated brine solution and dried over sodium sulfate. Solvents were removed under reduced pressure to afford a yellow solid that was purified via trituration from diethyl ether to afford 5-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-8,10-difluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one (2.63 g, 3.90 mmol) as a yellow solid. (ESIMS (M+H)+=675)

Aufarbeitung

  1. dissolutionhad completely dissolved
  2. temperatureThe resulting solution was cooled to room temperature
  3. washThe organic layer was washed with water and saturated brine solution
  4. dry with materialdried over sodium sulfate
  5. customSolvents were removed under reduced pressure
  6. customto afford a yellow solid
  7. customthat was purified via trituration from diethyl ether

Quellen und Nachweise

ORD-Eintrag
ord-1b6fa16d9e634e25beb9d4c923639d72
Quelldatensatz
uspto-grants-2011_07
Patentnummer
US07981903B2

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