M.W:300-400| Page 41 of 41 | Heterocyclic Building Blocks-Thiazines

New downstream synthetic route of 154127-42-1

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,(S)-4-Hydroxy-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazine-6-sulfonamide 1,1-dioxide,154127-42-1,its application will become more common.

A common heterocyclic compound, 154127-42-1,(S)-4-Hydroxy-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazine-6-sulfonamide 1,1-dioxide, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route. 154127-42-1

Prepare a 1L three-vial bottle equipped with a mechanical stirrer, a constant pressure low liquid funnel, and an ice water bath.Add compound of formula A (100 g, 0.28 mol) and acetonitrile (400 mL),Under N2 protection, stirring and cooling to 5 ~ 10 C,Then drop itTrimethyl orthoacetate(77.3g, 0.64mol),The rate of addition is such that the stability of the system does not exceed 15C.After the addition, remove the cooling and continue the reaction for 1 hour.TLC detected the disappearance of the starting material, creating a slightly more polar new point.Concentrate at normal pressure, recover the solvent and add the residue to DCM.Swirling to replace desolvation, and finally high vacuum drying for 1 hour,The residue is a compound of formula B-1Can be directly used in subsequent reactions without purificationThe reaction gave the crude product B-1 in equivalent yield.

Reference£º
Patent; Shanghai Bo Shirui Life Technology Co., Ltd.; Wang Dong; Wang Fangdao; Wang Meng; Cai Maojun; (16 pag.)CN107722043; (2018); A;,
Thiazine – an overview | ScienceDirect Topics
Thiazine | C4H5NS – PubChem

The origin of a common compound about 154127-41-0

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,154127-41-0,2-(3-Methoxypropyl)-4-oxo-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazine-6-sulfonamide 1,1-dioxide,its application will become more common.

A common heterocyclic compound, 154127-41-0,2-(3-Methoxypropyl)-4-oxo-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazine-6-sulfonamide 1,1-dioxide, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route. 154127-41-0

Step I: (S)-3,4-Dihydro-4-hydroxy-2-(3-methoxy)propyl-2H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide-1,1-di oxide To a solution of the product of Step H (2.6 g, 7.34 mmol) in THF (30 mL) at -78 C. was added a solution of (+)-beta-chlorodiisopinocampheylborane (11.8 g, 36.7 mmol) in THF (10 mL). The reaction mixture was allowed to warm to -20 C. and kept at this temperature for 4 days. Diethanolamine (4.2 mL, 44 mmol) was added to the reaction mixture and the solution stirred for 30 min, diluted with EtOAc (150 mL), washed with water (2*50 mL) and brine (2*50 mL), dried (MgSO4), and evaporated to a syrup which was purified by column chromatography [silica; CH30 OH/CH2 Cl2 (20:1)] to give 2.4 g (92%) of the desired compound as a colorless foam.

Reference£º
Patent; Alcon Laboratories, Inc.; US5378703; (1995); A;,
Thiazine – an overview | ScienceDirect Topics
Thiazine | C4H5NS – PubChem

A new synthetic route of (S)-4-Hydroxy-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazine-6-sulfonamide 1,1-dioxide

This compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,154127-42-1,(S)-4-Hydroxy-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazine-6-sulfonamide 1,1-dioxide,its application will become more common.

Step J: (+)-4-Ethylamino-3,4-dihydro-2-(3-methoxy)propyl-2H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide-1,1-dioxide hydrochloride To a solution of the product from Step I (2.4 g, 6.74 mmol) and triethylamine (3.8 mL, 27 mmol) in anhydrous tetrahydrofuran (20 mL) cooled to -20 C. was added tosyl chloride (2.6 g, 13.5 mmol); this mixture was allowed to warm to room temperature and stirred for 18 hr. The reaction mixture was cooled to -60 C. and ethylamine (10 mL) was added and the mixture was again allowed to warm to room temperature. After 18 hr the reaction mixture was diluted with ethyl acetate (200 mL), washed with a saturated aqueous solution of sodium bicarbonate (3*50 mL), dried (MgSO4), and evaporated to give the crude product which was purified by column chromatography [silica; CH3 OH/CH2 Cl2 (20:1)] to give 1.3 g (52%) of the desired amine. The free base was dissolved in ethanol (5 mL) and treated with a 2M solution of hydrochloric acid in ethanol (4 mL) at room temperature. Evaporation of the solvent provided a solid which was recrystallized from methanol: methylene chloride to give 950 mg (34%) of the desired product; mp 175-177 C.; [~]D +10.35 (C=1.00, H2 O). Analysis. Calculated for C12 H22 ClN3 O5 S3: C, 34.32; H, 5.28; N, 10.00 Found: C, 34.26; H, 5.23; N, 9.92., 154127-42-1

Reference£º
Patent; Alcon Laboratories, Inc.; US5378703; (1995); A;,
Thiazine – an overview | ScienceDirect Topics
Thiazine | C4H5NS – PubChem

Some scientific research about 154127-42-1

Step H: 4(R)-ethylamino-3,4-dihydro-2-(3-methoxypropyl)-2H-thieno[3,2-e]-l,2- thiazine-6-sulfonamide- 1,1 -dioxide (I); To a solution of IX (41 g, 0.12 moles) and triethylamine (33 ml. 0.24 moles) in anhydrous tetrahydrofuran (615 ml) cooled to 0 to 5 C was added a solution of tosyl chloride (44 g, 0.24 moles) in tetrahydrofuran (205 ml). The mixture was allowed to warm to room temperature and stirred for 18 hours. The reaction mixture was cooled to 0 to 50C and ethylamine gas was purged from its 70% aqueous solution (365 ml) below 10C. Reaction mixture was allowed to attain ambient temperature and stirred for 36 hours. The reaction mixture was concentrated and ethyl acetate (615 ml) was added to it. Further the organic layer was washed with water (410 ml). The concentrated ethyl acetate layer and MDC (615 ml) was added followed by cooling to temperature 0 to 50C and 6M hydrochloric acid (600 ml) was added. The reaction mixture was stirred for 1 h at 15 to 20C. Aqueous layer was washed with MDC (205 ml). pH of the aqueous solution was adjusted to 8 using sodium bicarbonate solution causing white solid to precipitate which was extracted with ethyl acetate (2 x 410 ml). The ethyl acetate layer was evaporated to dryness to yield crude Brinzolamide (29g, 66%). Material was recrystallized from ethanol. [Purity: greater than 99.5%, m.p. 125-1270C]

Reference£º
Patent; USV LIMITED; WO2008/62463; (2008); A2;,
Thiazine – an overview | ScienceDirect Topics
Thiazine | C4H5NS – PubChem

A new synthetic route of 154127-42-1

Compound B (50.0 g, 140.7 mmol) was added to 450 mL of acetonitrile, trimethyl orthoacetate (27.0 g, 225.1 mmol) and triethylamine (1.4 g, 14.0 mmol) were added with stirring, and the mixture was heated to 78C. , stirring for 5h,HPLC monitoring showed complete reaction and the HPLC monitoring results are shown in Table 1 (see FIG. 1).Cool to 40C, distill off under reduced pressure, and concentrate to a minimum volume.Compound C crude product was obtained.The crude compound C was dissolved in 180 mL of tetrahydrofuran, cooled to -10 DEG C, triethylamine (31.3 g, 309.5 mmol) was slowly added dropwise at a drip rate of 1 d/s, and the addition was completed at a drip rate of 3 d/s. 4- A solution of tosyl chloride (53.5 g, 280.6 mmol) in 70 mL of tetrahydrofuran. After the addition, the temperature was controlled at -4C, and the reaction was complete after about 3 hours.At a controlled temperature of 10 C. or less, a 70% aqueous solution of ethylamine (361.0 g, 5.6 M) was slowly added dropwise at a rate of 5 d/s. After the addition, the temperature was kept stirring at 12C and the reaction was complete after about 15 hours.The mixture was concentrated under reduced pressure to 70-80 mL, and the temperature was lowered to 0C. The temperature was controlled below 30C, and concentrated hydrochloric acid (12 mol/L) was added dropwise to adjust the pH to 1 to 2, and then about 14 mL of concentrated hydrochloric acid (12 mol/L) was added. The mixture was stirred at room temperature for 1 hour. The reaction was extracted twice with methyl tert-butyl ether (2*250 mL). The organic phases were combined and extracted once with dilute hydrochloric acid (1 mol/L, 100 mL). Combine the aqueous phases, slowly add sodium bicarbonate solids, adjust the pH to 5-6, add 150 mL of water, and adjust the pH to 7-8 with 7% sodium bicarbonate solution. After adjustment, stir at room temperature for 15 h and slowly crystallize. After filtration, the filter cake was rinsed with 30 mL of water and the cake was dried to obtain 35.4 g of product with a purity of 98.3%.Add 250 mL of dichloromethane, 25 mL of methanol to the filter mother liquor, stir, extract, separate, and concentrate the organic phase to dryness4.6 g of yellow viscous material was added and 10 mL of ethyl acetate was added. Heat to 70 ~ 75 C dissolved, slowly dropped to 0 ~ 10 C, stirring 1 ~ 2h, precipitation of a white solid, continue stirring 3 ~ 4h, filtration, with 3mL water filter cake, filter cake drying,Obtained product 2.4g, purity 97.3%.Combined, the purity was 98.1%, the total yield was 65.3%, the ignition residue was 0.08%, and the chiral purity was 99.7%.

Reference£º
Patent; Shandong Weizhi Pharmaceutical Co., Ltd.; Shanghai Weizhi Pharmaceutical Technology Co., Ltd.; Wang Jianhua; He Yigang; Wei Yanjun; Xing Yanping; Zhao Tianchang; (27 pag.)CN107759618; (2018); A;,
Thiazine – an overview | ScienceDirect Topics
Thiazine | C4H5NS – PubChem

The origin of a common compound about 154127-42-1

Reference£º
Patent; Alcon Laboratories, Inc.; US5378703; (1995); A;,
Thiazine – an overview | ScienceDirect Topics
Thiazine | C4H5NS – PubChem

Some scientific research about (S)-4-Hydroxy-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazine-6-sulfonamide 1,1-dioxide

154127-42-1 A common heterocyclic compound, 154127-42-1,(S)-4-Hydroxy-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazine-6-sulfonamide 1,1-dioxide, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.

To a solution of IX (41 g, 0.12 moles) and triethylamine (33 ml. 0.24 moles) in anhydrous tetrahydrofuran (615 ml) cooled to 0 to 5 C. was added a solution of tosyl chloride (44 g, 0.24 moles) in tetrahydrofuran (205 ml). The mixture was allowed to warm to room temperature and stirred for 18 hours. The reaction mixture was cooled to 0 to 5 C. and ethylamine gas was purged from its 70% aqueous solution (365 ml) below 10 C. Reaction mixture was allowed to attain ambient temperature and stirred for 36 hours. The reaction mixture was concentrated and ethyl acetate (615 ml) was added to it. Further the organic layer was washed with water (410 ml). The concentrated ethyl acetate layer and MDC (615 ml) was added followed by cooling to temperature 0 to 5 C. and 6M hydrochloric acid (600 ml) was added. The reaction mixture was stirred for 1 h at 15 to 20 C. Aqueous layer was washed with MDC (205 ml). pH of the aqueous solution was adjusted to 8 using sodium bicarbonate solution causing white solid to precipitate which was extracted with ethyl acetate (2*410 ml). The ethyl acetate layer was evaporated to dryness to yield crude Brinzolamide (29 g, 66%). Material was recrystallized from ethanol. [Purity: greater than 99.5%, m.p. 125-127 C.]

Reference£º
Patent; Sathe, Dhananjay Govind; Tarur, Radhakrishnan Venkatasubramanian; Bhise, Nandu Baban; Shinde, Ajit Bhaskar; Pardeshi, Santosh; US2010/9977; (2010); A1;,
Thiazine – an overview | ScienceDirect Topics
Thiazine | C4H5NS – PubChem