ChemicalBook CAS DataBase List 5-METHOXY-1,3-BENZOTHIAZOL-2-AMINE

5-METHOXY-1,3-BENZOTHIAZOL-2-AMINE synthesis

4synthesis methods

Product Name:5-METHOXY-1,3-BENZOTHIAZOL-2-AMINE
CAS Number:54346-87-1
Molecular formula:C8H8N2OS
Molecular Weight:180.23

37014-08-7

54346-87-1

1. Preparation of 5-methoxy-benzothiazol-2-ylamine: To a suspension of (3-methoxyphenyl)thiourea (1.822 g, 10 mmol) in dichloromethane (20 mL) was slowly added dropwise a solution of bromine (1.76 g, 11 mmol) in 10 mL of trichloromethane at 0 °C for 30 min. The reaction mixture was stirred at room temperature for 3 hours and then heated to reflux for 1 hour. After completion of the reaction, the precipitate was collected by filtration and washed with dichloromethane. The solid was suspended in saturated sodium bicarbonate solution and extracted with dichloromethane. The organic phases were combined, dried with magnesium sulfate and concentrated to give a white solid product (1.716 g, 95% yield). 2. Preparation of 2-amino-benzothiazol-5-ol: 5-methoxy-benzothiazol-2-ylamine (1.716g) obtained in the previous step was suspended in 16mL of 48% aqueous hydrobromic acid, and the reaction was heated in an oil bath at 105°C for 10 hours. After the reaction was cooled to room temperature, the precipitate was collected by filtration and washed with acetone. The solid in the filtrate was suspended in saturated sodium bicarbonate solution and extracted with dichloromethane. The organic phase was dried with magnesium sulfate and concentrated to give a white solid product (0.986 g, 63% yield). 3. Synthesis of N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[6-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea hydrochloride [Compound B12]: 2-amino-benzothiazol-5-ol obtained from the previous step was used as a raw material, and the reaction was carried out according to the literature method. The product was characterized by nuclear magnetic resonance hydrogen spectroscopy (DMSO-d6) and liquid chromatography-mass spectrometry (LC-MS): 1H NMR (DMSO-d6) δ 11.1 (br, 1H), 9.69 (br, 1H), 9.28 (br, 1H), 8.71 (s, 1H), 7.97 (d, 1H), 7.79 (d and s, 3H), 7.56 (d, 2H), 7.56 (d, 2H), 7.13 (d, 2H). 2H), 7.13 (dd, 1H), 6.53 (s, 1H), 4.56 (t, 2H), 3.98 (m, 2H), 3.82 (t, 2H), 3.65 (m, 2H), 3.55 (m, 2H), 3.25 (m, 2H), 1.31 (s, 9H); LC-MS: ESI 561 (M + H)+.

37014-08-7
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54346-87-1
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Yield: 95%

Reaction Conditions:

with bromine in dichloromethane;chloroform at 20; for 4 - 6 h;Heating / reflux;

Steps:

3.I
I. N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[6-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea hydrochloride [Compound B12] was also prepared by first preparing the benzothiazole starting material, 5 methoxy-benzothiazol-2-yl-amine: To prepare the 5-methoxy-benzothiazol-2-ylamine starting material: To a suspension of (3-methoxy-phenyl)-thiourea (1.822 g, 10 mmol) in CH2Cl2 (20 mL) at 0 C. was added dropwise a solution of bromine (1.76 g, 11 mmol) in 10 ml of trichloromethane over a period of thirty minutes. The reaction was stirred for 3 hours at room temperature then heated to 3 hours to reflux for one hour. The precipitate was filtered and washed with dichloromethane. The solid was suspended in saturated NaHCO3 and extracted with CH2Cl2. The extract was dried over MgSO4 and concentrated to give a white solid (1.716 g, 95%). To prepare the 2-amino-benzothiazol-5-ol: To a suspension of 5-methoxy-benzothiazol-2-ylamine in 16 mL of 48% HBr/H2O was heated to 105 C. in an oil bath for 10 hours. After the reaction was cooled to room temperature, the precipitate was collected by filtration and washed with acetone. The filtrate was suspended in saturated NaHCO3 and extracted with CH2Cl2. The extract was dried over MgSO4 and concentrated to give a white solid (0.986 g, 63%). N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[6-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea hydrochloride 2-amino-benzothiazol-5-ol from the previous step and following the method described in 1H NMR (DMSO-d6) ? 11.1 (br, 1H), 9.69 (br, 1H), 9.28 (br, 1H), 8.71 (s, 1H), 7.97 (d, 1H), 7.79 (d and s, 3H), 7.56 (d, 2H), 7.13 (dd, 1H), 6.53 (s, 1H), 4.56 (t, 2H), 3.98 (m, 2H), 3.82 (t, 2H), 3.65 (m, 2H), 3.55 (m, 2H), 3.25 (m, 2H), 1.31 (s, 9H); LC-MS: ESI 561 (M+H)+. [Compound B12]

References:

Bhagwat, Shripad;Chao, Qi;Grotzfeld, Robert M.;Patel, Hitesh K.;Sprankle, Kelly G. US2007/232604, 2007, A1 Location in patent:Page/Page column 40

27191-09-9 Synthesis