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

HRID 1432960노트

반응식

HRID 1432960 반응식
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

참가 물질

7

반응물 3

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

생성물 1

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

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 6422Trifluoroacetic acid용매HCID 18373917Acetonitrile--water (1/1)용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-b83b3fba851e4491b32cee272b747994
출처 데이터셋
uspto-grants-2009_11
특허 번호
US07612075B2

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