Name: 863028-98-2|4-(Methylamino)-2-(methylthio)-5-pyrimidinecarboxylic acid|95%
Brand: Ambeed
SKU: A266036
Rating: 98 (26 reviews)

1
[ 863028-98-2 ]
[ 863029-00-9 ]

Yield	Reaction Conditions	Operation in experiment
43%	Stage #1: 4-methylamino-2-methylsulfanylpyrimidine-5-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 4h; Stage #2: With ammonium hydroxide In N,N-dimethyl-formamide at 20℃; for 14h;

Reference： [1]Hisamichi, Hiroyuki; Naito, Ryo; Toyoshima, Akira; Kawano, Noriyuki; Ichikawa, Atsushi; Orita, Akiko; Orita, Masaya; Hamada, Noritaka; Takeuchi, Makoto; Ohta, Mitsuaki; Tsukamoto, Shin-Ichi [Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 16, p. 4936 - 4951]

2
[ 76360-82-2 ]
[ 863028-98-2 ]

Yield	Reaction Conditions	Operation in experiment
94%	With sodium hydroxide In ethanol at 50℃; for 1h;
80%	With water; sodium hydroxide In methanol at 20℃; for 20h; Inert atmosphere;
80%	With sodium hydroxide In methanol; water at 20℃; for 20h; Inert atmosphere;

70%

With lithium hydroxide In methanol; water at 60℃; for 3h;

25.2 Step 2: 4-(Methylamino)-2-(methylthio)pyrimidine-5-carboxylic acid: Lithium hydroxide (211 mg, 8.8 mmol) was added to ethyl 4-(methylamino)-2-(methylthio)pyrimidine-5-carboxylate (1.0 g, 4.4 mmol) in a mixture of methanol(8 mL) and water (4 mL) to give a white suspension. This was heated to 60 °C for 3 h and then concentrated to dryness under reduced pressure. The residue was re-dissolved in water (25 mL) and acidified with acetic acid to pH 5. The precipitated solid was isolated byfiltration, washed with water (2 x 10 mL) and freeze-dried to give the title compound (610 mg, 70%) as an off- white solid. ‘H NMR (500 MHz, DMSQ-d6): 6 13.10 (br s, 1H), 8.49 (s, 1H), 8.36 (br s, 1H), 2.98 (d, 3H), 2.49 (s, 3H). LCMS (Method A): RT = 0.52 mi m/z = 200[M+H].

Reference： [1]Hisamichi, Hiroyuki; Naito, Ryo; Toyoshima, Akira; Kawano, Noriyuki; Ichikawa, Atsushi; Orita, Akiko; Orita, Masaya; Hamada, Noritaka; Takeuchi, Makoto; Ohta, Mitsuaki; Tsukamoto, Shin-Ichi [Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 16, p. 4936 - 4951]
[2]Liang, Xiaofei; Liu, Xiaochuan; Wang, Beilei; Zou, Fengming; Wang, Aoli; Qi, Shuang; Chen, Cheng; Zhao, Zheng; Wang, Wenchao; Qi, Ziping; Lv, Fengchao; Hu, Zhenquan; Wang, Li; Zhang, Shanchun; Liu, Qingsong; Liu, Jing [Journal of Medicinal Chemistry, 2016, vol. 59, # 5, p. 1984 - 2004]
[3]Liang, Xiaofei; Lv, Fengchao; Wang, Beilei; Yu, Kailin; Wu, Hong; Qi, Ziping; Jiang, Zongru; Chen, Cheng; Wang, Aoli; Miao, Weili; Wang, Wenchao; Hu, Zhenquan; Liu, Juan; Liu, Xiaochuan; Zhao, Zheng; Wang, Li; Zhang, Shanchuan; Ye, Zi; Wang, Chu; Ren, Tao; Wang, Yinsheng; Liu, Qingsong; Liu, Jing [Journal of Medicinal Chemistry, 2017, vol. 60, # 5, p. 1793 - 1816]
[4]Current Patent Assignee: THE MCCLAY FOUNDATION - WO2015/19037, 2015, A1 Location in patent: Page/Page column 88

3
[ 863028-98-2 ]
2-(2-amino-ethylamino)-4-methylamino-pyrimidine-5-carboxylic acid amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; 1-hydroxybenzotriazole / dimethylformamide / 4 h / 20 °C 1.2: 43 percent / aqueous ammonia / dimethylformamide / 14 h / 20 °C 2.1: 28 percent / acetonitrile / 0.5 h / 20 °C

Reference： [1]Hisamichi, Hiroyuki; Naito, Ryo; Toyoshima, Akira; Kawano, Noriyuki; Ichikawa, Atsushi; Orita, Akiko; Orita, Masaya; Hamada, Noritaka; Takeuchi, Makoto; Ohta, Mitsuaki; Tsukamoto, Shin-Ichi [Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 16, p. 4936 - 4951]

4
[ 5909-24-0 ]
[ 863028-98-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 84 percent / toluene / 8 h / Heating 2: 94 percent / NaOH / ethanol / 1 h / 50 °C
	Multi-step reaction with 2 steps 1: triethylamine / tetrahydrofuran / 50 °C 2: lithium hydroxide / water; methanol / 3 h / 60 °C
	Multi-step reaction with 2 steps 1: triethylamine / tetrahydrofuran / 15 h / 0 - 20 °C / Inert atmosphere 2: sodium hydroxide; water / methanol / 20 h / 20 °C / Inert atmosphere

Multi-step reaction with 2 steps 1: triethylamine / tetrahydrofuran / 15 h / 0 - 20 °C / Inert atmosphere 2: sodium hydroxide / methanol; water / 20 h / 20 °C / Inert atmosphere

Reference： [1]Hisamichi, Hiroyuki; Naito, Ryo; Toyoshima, Akira; Kawano, Noriyuki; Ichikawa, Atsushi; Orita, Akiko; Orita, Masaya; Hamada, Noritaka; Takeuchi, Makoto; Ohta, Mitsuaki; Tsukamoto, Shin-Ichi [Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 16, p. 4936 - 4951]
[2]Current Patent Assignee: THE MCCLAY FOUNDATION - WO2015/19037, 2015, A1
[3]Liang, Xiaofei; Liu, Xiaochuan; Wang, Beilei; Zou, Fengming; Wang, Aoli; Qi, Shuang; Chen, Cheng; Zhao, Zheng; Wang, Wenchao; Qi, Ziping; Lv, Fengchao; Hu, Zhenquan; Wang, Li; Zhang, Shanchun; Liu, Qingsong; Liu, Jing [Journal of Medicinal Chemistry, 2016, vol. 59, # 5, p. 1984 - 2004]
[4]Liang, Xiaofei; Lv, Fengchao; Wang, Beilei; Yu, Kailin; Wu, Hong; Qi, Ziping; Jiang, Zongru; Chen, Cheng; Wang, Aoli; Miao, Weili; Wang, Wenchao; Hu, Zhenquan; Liu, Juan; Liu, Xiaochuan; Zhao, Zheng; Wang, Li; Zhang, Shanchuan; Ye, Zi; Wang, Chu; Ren, Tao; Wang, Yinsheng; Liu, Qingsong; Liu, Jing [Journal of Medicinal Chemistry, 2017, vol. 60, # 5, p. 1793 - 1816]

5
[ 863028-98-2 ]
4-(methylamino)-2-(methylthio)pyrimidine-5-carbonyl fluoride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With trifluoro-[1,3,5]triazine; triethylamine In dichloromethane at 20℃; for 2h;	25.3 Step 3: 4-(Methylamino)-2-(methylthio)pyrimidine-5- carbonyl fluoride: To a solution of 4-(methylamino)-2-(methylthio)pyrimidine-5-carboxylic acid (610 mg, 3.1mmol) and triethylamine (470 1L, 3.4 mmol) in anhydrous dichloromethane (6 mL) was added dropwise a solution of cyanuric fluoride (525 1L, 6.1 mmol) in anhydrous dichloromethane (3 mL) and the mixture stirred at RT for 2 h. The reaction mixture was diluted with dichloromethane (20 mL), washed with ice-cold water (2 x20 mL), dried over Na2SO4, filtered, and concentrated todryness under reduced pressure to give the title compound(555 mg, 90%) as an off-white solid. ‘H NMR (500 MHz,CDC13) : 6 8.56 (s, 1H), 7.60 (br s, 1H), 3.14 (d, 3H),2.57 (s, 3H) . LCMS (Method A) : = 1.05 mi m/z =202.15 [M+H].

Reference： [1]Current Patent Assignee: THE MCCLAY FOUNDATION - WO2015/19037, 2015, A1 Location in patent: Page/Page column 88; 89

6
[ 863028-98-2 ]
7-amino-6-(2-chlorophenyl)-8-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-5(8H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: trifluoro-[1,3,5]triazine; triethylamine / dichloromethane / 2 h / 20 °C 2.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.17 h / 0 - 20 °C 2.2: 1 h / 0 - 20 °C 2.3: 2 h / 20 °C