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

HRID 1432960Notes

Reaction equation

HRID 1432960 reaction equation
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

Participants

7

Reactant 3

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

Product 1

HCID 671086531-(4-Amino-quinazolin-7-ylmethyl)-4-[3-(5-chloro-thiophen-2-yl)-(E)-allyl]-piperazin-2-oneYield 38.7%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6422Trifluoroacetic acidSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-b83b3fba851e4491b32cee272b747994
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

Loading…