Potassium Carbonate → 1-(4-Amino-quinazolin-7-ylmethyl)-4-[3-(5-chloro-thiophen-2-yl)-(E)-allyl]-piperazin-2-one

HRID 1432960Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1432960
Cl.Cl.[NH2:3][C:4]1[C:13]2[C:8](=[CH:9][C:10]([CH2:14][N:15]3[CH2:20][CH2:19][NH:18][CH2:17][C:16]3=[O:21])=[CH:11][CH:12]=2)[N:7]=[CH:6][N:5]=1.Br[CH2:23]/[CH:24]=[CH:25]/[C:26]1[S:27][C:28]([Cl:31])=[CH:29][CH:30]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O.C(#N)C.FC(F)(F)C(O)=O>[NH2:3][C:4]1[C:13]2[C:8](=[CH:9][C:10]([CH2:14][N:15]3[CH2:20][CH2:19][N:18]([CH2:23]/[CH:24]=[CH:25]/[C:26]4[S:27][C:28]([Cl:31])=[CH:29][CH:30]=4)[CH2:17][C:16]3=[O:21])=[CH:11][CH:12]=2)[N:7]=[CH:6][N:5]=1

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 217085162-(3-Bromo-(E)-propenyl)-5-chloro-thiopheneHCID 690243421-(4-Aminoquinazoline-7-ylmethyl)piperazine-2-one bishydrochloride

Produkt 1

HCID 671086531-(4-Amino-quinazolin-7-ylmethyl)-4-[3-(5-chloro-thiophen-2-yl)-(E)-allyl]-piperazin-2-oneAusbeute 38,7 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 6422Trifluoroacetic acidLösungsmittelHCID 18373917Acetonitrile--water (1/1)Lösungsmittel

Versuchsvorschrift

To a solution of 1-(4-amino-quinazolin-7-ylmethyl)-piperazin-2-one bishydrochloride (100 mg, 0.31 mmol), EXAMPLE 72, in 3 mL of DMF is added 2-(3-bromo-(E)-propenyl)-5-chloro-thiophene (73 mg, 0.31 mmol), prepared as described in EXAMPLE 17., and K2CO3 (0.21 g, 1.54 mmol). The solution is stirred at room temperature for 16 hours. After this time, the solution is diluted with water/acetonitrile and neutralized with trifluoroacetic acid. The crude material is purified by RP-HPLC eluting in a gradient of 10% CH3CN/H2O (0.1% TFA) to 60% CH3CN/H2O (0.1% TFA) and the appropriate product fractions are combined and lyopholized to give the title compound (80 mg, 0.12 mmol) as a white solid. 1H NMR (DMSO-d6, 300 MHz) δ9.76 (bs, 2H), 8.81 (s, 1H), 8.40 (d, 1H), 7.70 (s, 1H), 7.62 (dd, 1H), 7.10 (m, 2H), 6.90 (d, 1H), 6.05 (dt, 1H), 4.80 (s, 2H), 3.77 (m, 4H), 3.50 (m, 2H), 3.37 (m, 2H), ESI MS, [M+H]+=414,416 (Cl pattern). Anal. (C20H20ClN5OS.2.0TFA.1.1H2O) C, H, N.

Aufarbeitung

  1. customprepared
  2. customThe crude material is purified by RP-HPLC
  3. washeluting in a gradient of 10% CH3CN/H2O (0.1% TFA) to 60% CH3CN/H2O (0.1% TFA)

Quellen und Nachweise

ORD-Eintrag
ord-b83b3fba851e4491b32cee272b747994
Quelldatensatz
uspto-grants-2009_11
Patentnummer
US07612075B2

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