Hydrochloric Acid → 8-fluoro-5-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-3-[(4-methylphenyl)sulfonyl]pyrrolo [2',3':4,5]pyrimido[6,1-b]quinazolin-7(3H)-one

HRID 1014429Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1014429
Cl[C:2]1[N:3]=[C:4]([NH:21][C:22]2[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:23]=2[C:24](N)=[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.[CH3:32][CH:33]([N:35]1[CH2:40][CH2:39][N:38]([C:41]2[CH:46]=[CH:45][C:44]([NH2:47])=[C:43]([O:48][CH3:49])[CH:42]=2)[CH2:37][CH2:36]1)[CH3:34].[I-].[K+].Cl>C(O)C(F)(F)F.O1CCOCC1.C(=O)(O)[O-].[Na+].C(Cl)Cl>[F:31][C:27]1[CH:28]=[CH:29][CH:30]=[C:22]2[C:23]=1[C:24](=[O:25])[N:3]1[C:2]([NH:47][C:44]3[CH:45]=[CH:46][C:41]([N:38]4[CH2:39][CH2:40][N:35]([CH:33]([CH3:32])[CH3:34])[CH2:36][CH2:37]4)=[CH:42][C:43]=3[O:48][CH3:49])=[N:7][C:6]3[N:8]([S:11]([C:14]4[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=4)(=[O:13])=[O:12])[CH:9]=[CH:10][C:5]=3[C:4]1=[N:21]2

Komponenten

8

Edukt 4

HCID 313Hydrochloric Acid2×HCID 4875Potassium Iodide2×HCID 457907394-(4-Isopropylpiperazin-1-YL)-2-methoxyphenylamineHCID 866441882-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide

Produkt 1

HCID 673164628-fluoro-5-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-3-[(4-methylphenyl)sulfonyl]pyrrolo [2',3':4,5]pyrimido[6,1-b]quinazolin-7(3H)-oneAusbeute 99 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 64092,2,2-TrifluoroethanolLösungsmittelHCID 312751,4-DioxaneLösungsmittel2×HCID 23716255Sodium bicarbonate methylene chlorideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of 2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide (5.50 g, 11.98 mmol), [4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amine (4.5 g, 18 mmol, 1.50 equiv.), and potassium iodide (<20 mg) in trifluoroethanol (200 mL) in a 300 mL sealed tube was added hydrochloric acid as a 4.0M solution in dioxane (12 mL, 48 mmol, 4 equiv.). The vessel was sealed and the resulting suspension was stirred rapidly at 80° C. for 12 hours. TLC/LCMS analysis indicates starting material still remains, so additional hydrochloric acid (5 mL as a 4.0M solution in dioxane) and potassium iodide (<20 mg) were added and heating was continued. Three such reactions were cooled and poured directly in saturated sodium bicarbonate/methylene chloride. The organic layer was collected, concentrated under reduced pressure, and then resuspended in diethylether. Sonication for 10 minutes was followed by filtration to give crude 8-fluoro-5-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one as an orange solid with sufficient purity for use in the next transformation (23.5 g, ca 99% yield, purity 85-90%). ESIMS (M+H)+=655.

Aufarbeitung

  1. customThe vessel was sealed
  2. temperatureheating
  3. temperatureThree such reactions were cooled
  4. customThe organic layer was collected
  5. concentrationconcentrated under reduced pressure
  6. customSonication for 10 minutes
  7. filtrationwas followed by filtration

Quellen und Nachweise

ORD-Eintrag
ord-028c602b3b3147b2920f8f3e11a5d6ed
Quelldatensatz
uspto-grants-2011_07
Patentnummer
US07981903B2

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