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Chemical Structure| 425638-73-9 Chemical Structure| 425638-73-9

Structure of 425638-73-9

Chemical Structure| 425638-73-9

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Product Details of [ 425638-73-9 ]

CAS No. :425638-73-9
Formula : C15H19N5O
M.W : 285.34
SMILES Code : O=C(N)CC1=C2C=CC=CC2=NC(N3CCN(C)CC3)=N1

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Application In Synthesis of [ 425638-73-9 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 425638-73-9 ]

[ 425638-73-9 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 109-01-3 ]
  • [ 425638-74-0 ]
  • [ 425638-73-9 ]
YieldReaction ConditionsOperation in experiment
70% In 1-methyl-pyrrolidin-2-one; at 60℃; for 0.5h;Inert atmosphere; 2-(2-(4-Methylpiperazin-1-yl)quinazolin-4-yl)acetamide To solution of 2-(2-chloroquinazolin-4-yl) acetamide (8.20 g, 37.0 mmol, Preparation #D.1) in NMP (74 mL) was added 1-methylpiperazine (20.5 mL, 185 mmol). The reaction mixture was heated to about 60 C. and stirred for about 30 min. The reaction was cooled to ambient temperature, EtOAc (90 mL) was added and the mixture was stirred at ambient temperature for about 2 h. The reaction was cooled to about 0 C. and the solids were collected by filtration washing with EtOAc to give 2-(2-(4-methylpiperazin-1-yl)quinazolin-4-yl)acetamide (7.37 g, 70% yield): LC/MS (Table 1, Method c) Rt=1.41 min; MS m/z: 286 (M+H)+.
55% In 1-methyl-pyrrolidin-2-one; at 50℃; for 0.5h; Lambda/, nu-dimethylaniline (33.4 g, 276 mmol, 1 .0 eq) was added dropwise to a solution of 2,4 (1 H, 3H)-quinazolinedione (50 g, 276 mmol, 1 .0 eq) in POCI3 (300 ml) and the mixture was heated to reflux for 3 hrs. The solution was cooled to room temperature, poured onto ice water and the resulting precipitate was filtered off and washed with water. The solid was dissolved in EtOAc and washed with water and brine. The organic fraction was dried over Na2S04, filtered, concentrated under reduced pressure, and washed with petroleum ether to give the corresponding dichloro-derivative (20 g, 34% yield).Ethyl-3-oxobutanoate (31.2 g, 240 mmol, 2.0 eq) was added dropwise to a suspension of NaH (6 g, 156 mmol, 1 .3 eq) in THF (520 ml) at 0 C. After stirring at 0 C for 1 h and removal of THF under reduced pressure, a solution of 2,4-dichloroquinazoline (24 g, 120 mmol, 1.0 eq) in toluene (350 ml) was added and the reaction mixture was heated to reflux for 30 min. After removal of toluene under reduced pressure, NH4OH (320 ml) was added. After stirring for 20 min, the mixture was concentrated to remove NH4OH. EtOAc (100 ml) and water (50 ml) were added to the mixture, that was filtered to give 2-(2- chloroquinazolin-4-yl)acetamide (14.4 g, 54 % yield).1 -Methylpiperazine (34 g, 339 mmol, 5.0 eq) was added to a solution of 2-(2- chloroquinazolin-4-yl)acetamide (14.4 g, 65 mmol, 1.0 eq) in NMP (250 ml) and stirred at 50 C for 30 min. After cooling to room temperature, EtOAc (100 ml) was added and the suspension was filtered to give 2-(2-(4-methylpiperazin-1 -yl)quinazolin-4-yl)acetamide (10.5 g, 55 % yield).fert-BuOK (215 ml_, 121 mmol, 3.0 eq) was added to a solution of 2-(2-(4-methylpiperazin- 1 -yl)quinazolin-4-yl)acetamide (10.5 g, 36.8 mmol, 1.0 eq) and Intermediate 2 (10.5 g, 40.5 mmol, 1.1 eq) in anhydrous THF (250 ml) at room temperature and the mixture was stirred for about 30 min, quenched with water, extracted with EtOAc, washed with brine, dried over Na2S04, concentrated and purified by column chromatography (silicagel) to give the methyl-ester of intermediate 8 (1 1 g, 60 % yield).
In 1-methyl-pyrrolidin-2-one; ethyl acetate; c) <strong>[425638-74-0]2-(2-chloro-quinazolin-4-yl)-acetamide</strong> (221 mg, 1.0 mmol) is dissolved in 1-methyl-2-pyrrolidinone (2.0 mL) and N-methylpiperazine (555 muL, 5.0 eq.) is added. The mixture is heated 45 min. at 50 C. AcOEt is added and the suspension is filtered to afford 2-[2-(4-methyl-piperazin-1-yl)-quinazolin-4-yl]-acetamide as a white solid. ESI-MS: 284 [M-H]+, 241; 1H NMR (DMSO, 400 MHz) delta 2.24 (s, 3H), 2.40 (m, 4H), 3.86 (m, 4H), 3.98 (s, 2H), 7.12 (brs, 1H), 7.24 (dd, J=8.2, 7.5 Hz, 1H), 7.49 (d, J=8.4 Hz, 1H), 7.63-7.72 (m, 2H), 7.95 (d, J=8.2 Hz, 1H);
  • 2
  • [ 425638-73-9 ]
  • [ 18372-22-0 ]
  • [ 64-19-7 ]
  • 3-(1H-indol-3-yl)-4-[2-(4-methyl-piperazin-1-yl)-quinazolin-4-yl]-1H-pyrrole-2,5-dione acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
87.7% EXAMPLE 1:Preparation of polymorph A2-[2-(4-methyl-piperazin-1-yl)-quinazolin-4-yl]-acetamide (4.7 mg, 16.3 mmol) and 3- indoleglyςxylic acid methyl ester (4.35 mg, 1.3 eq.) are dissolved in THF (55 ml_). To the suspension is added dropwise a 20% solution of t-BuOK in THF (46.5 g, 5.1 eq.) at -5C. The mixture is stirred at 0-50C for 8h and the conversion is checked by a PSC. After the conversion is complete, the reaction mixture is quenched with a mixture of 10% sodium chloride in water (50 ml) and acetic acid (5g). Subsequent the aqueous layer is extracted with ethyl acetate (50 ml). The organic layer is extracted twice with 5% aqueous sodium bicarbonate (2x50ml), followed by concentration to 40 ml residual volume. To the residue ethyl acetate (50 ml) is added and subsequently is distilled off. This procedure is carried out four times. To the distillation residue (40 ml) ethaϖol is added (30 ml). The red solution is heated to 700C over a period of 30 minutes and acetic acid (4g) is added. After seeding the reaction is stirred at 700C for 90 minutes. The mixture is cooled to 300C over a period of 60 minutes and is stirred additionally for 30 minutes before it is cooled to 20C over a period of 90 minutes. After 14h at 200C the suspension is filtered, washed once with TBME (15ml) and once with a mixture TBME (13.5ml) - ethanol (1.5ml). After drying at 5OC under reduced pressure for 2h, the product is obtained in 87.7% yield as an orange crystalline solid. 1H NMR (DMSO, 400 MHz) δ 1.92 (s, 3H), 2.13 (s, 3H), 2.17 (m, 4H), 2.51 (m, 1H), 3.69 (m, 4H), 6.35 (d, J = 8.0 Hz, 1H), 6.64 (dd, J = 7.8, 7.4 Hz, 1 H), 7.02 (dd, J = 7.6, 7.4 Hz1 1H)1 7.10 (dd, J = 7.8, 7.2 Hz, 1H), 7.38 (d, J = 8.2 Hz, 1H), 7.53 (d, J = 8.4 Hz, 1H)1 7.63-7.73 (m, 2H), 8.13 (s, 1H), 11.29 (br s, 1H), 12.01 (br s, 1H).
 

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