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

HRID 1432960ノート

反応式

HRID 1432960 の反応式
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

参加物

7

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 6422Trifluoroacetic acid溶媒HCID 18373917Acetonitrile--water (1/1)溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-b83b3fba851e4491b32cee272b747994
出典データセット
uspto-grants-2009_11
特許番号
US07612075B2

反応ノート

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