Category: 1195768-23-0

Reference of 1195768-23-0 , The common heterocyclic compound, 1195768-23-0, name is N-(3-(2-(tert-Butyl)-5-(2-chloropyrimidin-4-yl)thiazol-4-yl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide, molecular formula is C23H18ClF3N4O2S2, 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.

Step D: A/-{3-[5-(2-amino-4-pyhmidinyl)-2-(1 ,1 -dimethylethyl)-1 ,3-thiazol-4-yl]-2- fluorophenyl}-2,6-difluorobenzenesulfonannideIn 1 gal pressure reactor, a mixture of A/-{3-[5-(2-chloro-4-pyrinnidinyl)-2-(1 ,1 – dimethylethyl)-1 ,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide (120 g) prepared in accordance with Step C, above, and ammonium hydroxide (28-30%, 2.4 L, 20 vol) was heated in the sealed pressure reactor to 98-103 C and stirred at this temperature for 2 hours. The reaction was cooled slowly to room temperature (20 C) and stirred overnight. The solids were filtered and washed with minimum amount of the mother liquor and dried under vacuum. The solids were added to a mixture of EtOAc (15 vol)/ water (2 vol) and heated to complete dissolution at 60-70 C and the aqueous layer was removed and discarded. The EtOAC layer was charged with water (1 vol) and neutralized with aq. HCI to ~pH 5.4-5.5. and added water (1 vol). The aqueous layer was removed and discarded at 60-70 C. The organic layer was washed with water (1 vol) at 60-70 C and the aqueous layer was removed and discarded. The organic layer was filtered at 60 C and concentrated to 3 volumes. EtOAc (6 vol) was charged into the mixture and heated and stirred at 72 C for 10 min , then cooled to 20C and stirred overnight. EtOAc was removed via vacuum distillation to concentrate the reaction mixture to ~3 volumes. The reaction mixture was maintained at ~65-70C for ~30mins. Product crystals having the same crystal form as those prepared in Example 58b (and preparable by the procedure of Example 58b), above, in heptanes slurry were charged. Heptane (9 vol) was slowly added at 65-70 C. The slurry was stirred at 65-70 C for 2- 3 hours and then cooled slowly to 0-5C. The product was filtered, washed withEtOAc/heptane (3/1 v/v, 4 vol) and dried at 45C under vacuum to obtain A/-{3-[5-(2- amino-4-pyrimidinyl)-2-(1 ,1 -dimethylethyl)-1 ,3-thiazol-4-yl]-2-fluorophenyl}-2,6- difluorobenzenesulfonamide (102.3 g, 88%).

The synthetic route of 1195768-23-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXOSMITHKLINE LLC; DUMBLE, Melissa; KUMAR, Rakesh; LAQUERRE, Sylvie; LEBOWITZ, Peter; WO2011/47238; (2011); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Synthetic Route of 1195768-23-0, Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps,and cheap raw materials. 1195768-23-0, name is N-(3-(2-(tert-Butyl)-5-(2-chloropyrimidin-4-yl)thiazol-4-yl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide. A new synthetic method of this compound is introduced below.

Step D : N- { 3 – [ 5-(2-amino-4-pyrimidiny l)-2-( 1 , 1 -dimethy lethyl)- 1 ,3 -thiazol-4-yl] -2- fluorophenyl} -2,6-difluorobenzenesulfonamide: In 1 gal pressure reactor, a mixture of N- {3-[5-(2-chloro-4-pyrimidinyl)-2-(l,l- dimethylethyl)-l,3-thiazol-4-yl]-2-fluorophenyl} -2,6-difluorobenzenesulfonamide (120 g) prepared in accordance with Step C, above, and ammonium hydroxide (28-30%, 2.4 L, 20 vol) was heated in the sealed pressure reactor to 98-103 C and stirred at this temperature for 2 hours. The reaction was cooled slowly to room temperature (20 C) and stirred overnight. The solids were filtered and washed with minimum amount of the mother liquor and dried under vacuum. The solids were added to a mixture of EtOAc (15 vol)/ water (2 vol) and heated to complete dissolution at 60-70 C and the aqueous layer was removed and discarded. The EtOAC layer was charged with water (1 vol) and neutralized with aq. HC1 to ~pH 5.4-5.5. and added water (lvol). The aqueous layer was removed and discarded at 60-70 C. The organic layer was washed with water (1 vol) at 60-70 C and the aqueous layer was removed and discarded. The organic layer was filtered at 60 C and concentrated to 3 volumes. EtOAc (6 vol) was charged into the mixture and heated and stirred at 72 C for 10 min , then cooled to 20C and stirred overnight. EtOAc was removed via vacuum distillation to concentrate the reaction mixture to ~3 volumes. The reaction mixture was maintained at ~65-70C for ~30mins. Product crystals having the same crystal form as those prepared in Example 58b (and preparable by the procedure of Example 58b), above, in heptanes slurry were charged. Heptane (9 vol) was slowly added at 65-70 C. The slurry was stirred at 65-70 C for 2-3 hours and then cooled slowly to 0-5C. The product was filtered, washed with EtO Ac/heptane (3/1 v/v, 4 vol) and dried at 45 C under vacuum to obtain N- {3 – [5 -(2-amino-4-pyrimidinyl)-2-( 1 , 1 -dimethylethyl)- 1 , 3 -thiazol-4-yl] -2- fluorophenyl}-2,6-difluorobenzenesulfonamide (102.3 g, 88%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,1195768-23-0, its application will become more common.

Reference:
Patent; NOVARTIS AG; CAPONIGRO, Giordano; HORN-SPIROHN, Thomas; LEHAR, Joseph; (49 pag.)WO2017/37587; (2017); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Adding a certain compound to certain chemical reactions, such as: 1195768-23-0, N-(3-(2-(tert-Butyl)-5-(2-chloropyrimidin-4-yl)thiazol-4-yl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound, Recommanded Product: N-(3-(2-(tert-Butyl)-5-(2-chloropyrimidin-4-yl)thiazol-4-yl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide, blongs to pyrimidines compound. Recommanded Product: N-(3-(2-(tert-Butyl)-5-(2-chloropyrimidin-4-yl)thiazol-4-yl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide

Preparation Example 1 The preparation of the Known Crystal Form 1: Refer to the preparation method described in example 58a of patent document WO2009/137391A2 or U.S. Pat. No. 7,994,185B2, with the details as follows: Add N-{3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide (196 mg, 0.364 mmol) and 7M methanol solution of ammonia (8 ml, 56 mmol) into a 25 mL autoclave, heat to 90 C. and react for 24 h; when the TLC shows the raw material is completely reacted, cool the above reaction system to room temperature, filter to get N-{3-[5-(2-amino-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide (i.e. Dabrafenib). 1H-NMR (400 MHz, DMSO-d6) delta ppm 10.83 (s, 1H), 7.93 (d, J=5.2 Hz, 1H), 7.55-7.70 (m, 1H), 7.35-7.43 (m, 1H), 7.31 (t, J=6.3 Hz, 1H), 7.14-7.27 (m, 3H), 6.70 (s, 2H), 5.79 (d, J=5.13 Hz, 1H), 1.35 (s, 9H). The XPRD pattern is as shown in FIG. 25 and is substantially the same as that of the Known Crystal Form 1 of Dabrafenib prepared in example 58a of patent document U.S. Pat. No. 7,994,185B2. The PLM plot is as shown in FIG. 26. It shows small block-shaped crystals. PSD shows: D10, D50 and D90 are 40 mum, 104 mum and 151 mum, respectively. The dynamic vapor sorption isothermal is as shown in FIG. 27. It shows: the weight change is 1.9% between 20% RH80% RH.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,1195768-23-0, N-(3-(2-(tert-Butyl)-5-(2-chloropyrimidin-4-yl)thiazol-4-yl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide, and friends who are interested can also refer to it.

Reference:
Patent; Hangzhou Pushai Pharmaceutical Technology Co., LTD.; LAO, Haiping; SHENG, Xiaoxia; Sheng, Xiaohong; US2015/307484; (2015); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Adding a certain compound to certain chemical reactions, such as: 1195768-23-0, N-(3-(2-(tert-Butyl)-5-(2-chloropyrimidin-4-yl)thiazol-4-yl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound, 1195768-23-0, blongs to pyrimidines compound. SDS of cas: 1195768-23-0

A suspension of N-(3-(2-(tert-butyl)-5-(2-chloropyrimidin-4-yl)thiazol-4-yl)-2- fluorophenyl)-2,6-difluorobenzenesulfonamide (50.0mg, 0.092mmol) and aniline (9.0mg, 0.097mmol) in iPrOH (lmL), in presence of catalytic concentrated HC1, was stirred at 100C for lh, then at 80C overnight. The mixture was concentrated under reduced pressure. The residue was partitioned between EtOAc and saturated aqueous sodium bicarbonate. The organic layer was washed with brine, dried over sodium sulphate, filtered and the filtrate was concentrated under vacuum. Purification by flash chromatography on silica gel (cHex-EtOAc, 1/0 to 0/1) afforded the title compound 1 (40mg, 72%). lU NMR (CDC13): 8.09 (d, 1H, J = 5.2 Hz); 7.84 (bs, 1H); 7.72 (m, 1H); 7.48 (d, 2H, J = 7.7Hz); 7.44-7.36 (m, 3H); 7.29 (t, 2H, J = 7.5Hz); 7.24 (t, 1H, J = 7.3Hz); 7.02 (t, 1H, J = 7.7Hz); 6.92 (t, 2H, J = 8.7Hz); 6.28 (d, 1H, J = 5.2Hz); 1.48 (s, 9H). LC/MS (ES+): 596.2 (M+l).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,1195768-23-0, its application will become more common.

Reference:
Patent; CELLIPSE; PRUDENT, Renaud; PAUBLANT, Fabrice; (74 pag.)WO2018/55097; (2018); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia