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

HRID 1014442Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1014442
Cl.[CH3:2][O:3][C:4]1[CH:10]=[C:9]([N:11]2[CH2:16][CH2:15][CH:14]([N:17]3[CH2:22][CH2:21][N:20]([S:23]([CH3:26])(=[O:25])=[O:24])[CH2:19][CH2:18]3)[CH2:13][CH2:12]2)[CH:8]=[CH:7][C:5]=1[NH2:6].Cl[C:28]1[N:29]=[C:30]([NH:47][C:48]2[CH:56]=[CH:55][CH:54]=[C:53]([F:57])[C:49]=2[C:50](N)=[O:51])[C:31]2[CH:36]=[CH:35][N:34]([S:37]([C:40]3[CH:45]=[CH:44][C:43]([CH3:46])=[CH:42][CH:41]=3)(=[O:39])=[O:38])[C:32]=2[N:33]=1.Cl.O1CCOCC1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[F:57][C:53]1[CH:54]=[CH:55][CH:56]=[C:48]2[C:49]=1[C:50](=[O:51])[N:29]1[C:28]([NH:6][C:5]3[CH:7]=[CH:8][C:9]([N:11]4[CH2:16][CH2:15][CH:14]([N:17]5[CH2:18][CH2:19][N:20]([S:23]([CH3:26])(=[O:25])=[O:24])[CH2:21][CH2:22]5)[CH2:13][CH2:12]4)=[CH:10][C:4]=3[O:3][CH3:2])=[N:33][C:32]3[N:34]([S:37]([C:40]4[CH:41]=[CH:42][C:43]([CH3:46])=[CH:44][CH:45]=4)(=[O:38])=[O:39])[CH:35]=[CH:36][C:31]=3[C:30]1=[N:47]2

Komponenten

7

Edukt 5

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 673170002-(Methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}aniline hydrochlorideHCID 866441882-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide

Produkt 1

HCID 594419478-fluoro-5-[(2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-3-[(4-methylphenyl)sulfonyl]pyrrolo[2',3':4,5]pyrimido[6,1-b]quinazolin-7(3H)-oneAusbeute 89,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of 2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}aniline hydrochloride (3 g, 7.41 mmol) and 2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide (3 g, 6.52 mmol) in trifluroroethanol (200 mL) and HCl in dioxane (14.16 ml, 56.6 mmol) and KI (300 mg, 1.807 mmol) was stirred at 90° C. in a 300 mL pressure vessel behind a blast shield for 15 hours. After cooling to rt, the solution was neutralized with aqueous NaHCO3 (400 mL), the black suspension was added to CH2Cl2 (500 mL), and the layers separated. Addition of brine (200 mL) helped to separate the organic and aqueous layers. The organic layers were concentrated under reduced pressure and then suspended in CH2Cl2 (20 mL) and Et2O (150 mL). The solid was filtered to obtain 8-fluoro-5-[(2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one as brown powder (4.5 g, 5.81 mmol, 89% yield). This material was used without further purification. ESIMS (M+H)+=775.32 (100%).

Aufarbeitung

  1. customthe layers separated
  2. additionAddition of brine (200 mL)
  3. customto separate the organic and aqueous layers
  4. concentrationThe organic layers were concentrated under reduced pressure
  5. filtrationThe solid was filtered

Quellen und Nachweise

ORD-Eintrag
ord-9978f92389db4ca2914063509864345c
Quelldatensatz
uspto-grants-2011_07
Patentnummer
US07981903B2

Notizen zur Reaktion

Wird geladen…