39065-95-7 Archives - Chlorides-buliding-blocks

September 16, 2021 News Some tips on 39065-95-7

The synthetic route of 39065-95-7 has been constantly updated, and we look forward to future research findings.

Application of 39065-95-7, A common heterocyclic compound, 39065-95-7, name is 4-(Chlorodifluoromethoxy)aniline, molecular formula is C7H6ClF2NO, 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 mixture of 1,2-dimethyl-4-(pyrimidin-5-yl)-1H-benzo[d]imidazole-6-carboxylic acid (4d, 15 mg, 0.056 mmol, 1 eq) and HATU (25.51 mg, 0.067 mmol, 1.2 eq), DIPEA (14.45 mg, 0.112 mmol, 19.48 uL, 2 eq) in DMF (1 mL) at 20 C. was added 4-[chloro(difluoro)methoxy]aniline (1h, 16.24 mg, 0.084 mmol, 1.5 eq). The mixture was stirred at 20 C. for 16 hours. The mixture was concentrated in vacuo. LCMS showed desired MS. The mixture was poured into water and extracted with EtOAc, and the combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated in vacuo to give the crude product. The residue was purified by prep-HPLC (TFA condition, column: Nano-Micro UniSil 5-100 C18 ULTRA 100*250 mm 5 um; mobile phase: [water (0.1%TFA)-ACN]; B %: 25%-50%, 11 min) to afford the title compound 4 as a white solid. MS mass calculated for [M+H]+ (C21H16ClF2N5O2) requires m/z 444.1, LCMS found m/z 444.1. 1H NMR (400 MHz, MeOD-d4) delta 9.33-9.25 (m, 3H), 8.48 (s, 1H), 8.25 (s, 1H), 7.88 (d, J=9.0 Hz, 2H), 7.33 (d, J=8.8 Hz, 2H), 4.07 (s, 3H), 2.85 (s, 3H).

The synthetic route of 39065-95-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Terns, Inc.; ROMERO, F. Anthony; KIRSCHBERG, Thorsten A.; HALCOMB, Randall; XU, Yingzi; (144 pag.)US2020/87283; (2020); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

9/14/2021 News Share a compound : 39065-95-7

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4-(Chlorodifluoromethoxy)aniline, its application will become more common.

Related Products of 39065-95-7,Some common heterocyclic compound, 39065-95-7, name is 4-(Chlorodifluoromethoxy)aniline, molecular formula is C7H6ClF2NO, 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.

A stirred solution of 6-hydroxy-5-iodonicotinic acid (40 g) and DMF (3.51 mL) in toluene (315 mL) was treated dropwise with SOd2 (43.9 mL) at RT and then stirred at 85C for 2.5 h. The solvent was evaporated off under reduced pressure and the residue was redissolved in DCM (315 mL). The solution was cooled in an icy water bath and to this solution a mixture of 4-(chlorodifluoromethoxy)aniline (26 .3 g) and Et3N (63 mL) in DCM (315 mL) was added dropwise. The mixture was stirred at rt for 1 hr. Then a saturated aqueous solution of NaHCO3 was added and the mixture was stirred at rt for 10 mm and a solid was formed. The mixture was then diluted with 315 mL of hexane and filtered to collect the white solid, washed with more water and air dried to afford 6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-iodonicotinamide (55.97 g). (Rt = 2.28 mi +ESI m/z: MH+ = 459.0).

Reference:
Patent; ASTAR BIOTECH LLC; LI, Lianhai; YU, Chunrong; HUANG, Haihong; (94 pag.)WO2017/186148; (2017); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

9/2/2021 News Brief introduction of 39065-95-7

Electric Literature of 39065-95-7,Some common heterocyclic compound, 39065-95-7, name is 4-(Chlorodifluoromethoxy)aniline, molecular formula is C7H6ClF2NO, 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 (1R,4R)-9-bromo-4-hydroxy-1-methyl-1,2,3,4-tetrahydrobenzo[4,5]imidazo [1,2-a]pyridine-7-carboxylic acid (49h, 10 mg, 0.031 mmol), 4-[chloro(difluoro)methoxy]aniline (1h, 7.14 mg, 0.037 mmol) in DMF (1 mL) was added HATU (14.03 mg, 0.037 mmol) and DIEA (11.92 mg, 0.092 mmol, 16.07 uL). The mixture was stirred at 15 C. for 5 hr. LCMS showed desired ms was detected. TLC (ethyl acetate_methanol=10:1, Rf=0.40) showed a new spot was formed. The reaction mixture was concentrated under reduced pressure to remove solvent. The residue was diluted with H2O (10 mL) and extracted with EtAOc (10 mL*3). The combined organic layers were washed with brine, dried over Ns2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep-TLC (SiO2, ethyl acetate_methanol=10:1) to give 49i as a white solid. 1H NMR (400 MHz, CDCl3-d) delta 8.09 (d, J=1.3 Hz, 1H), 8.00 (d, J=1.3 Hz, 1H), 7.71 (d, J=8.9 Hz, 2H), 7.25 (s, 1H), 5.46 (br t, J=5.8 Hz, 1H), 5.18 (br s, 1H), 2.76-2.60 (m, 1H), 2.39-2.17 (m, 2H), 1.96-1.86 (m, 1H), 1.53 (d, J=6.6 Hz, 3H).

Simple exploration of 39065-95-7

The synthetic route of 39065-95-7 has been constantly updated, and we look forward to future research findings.

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. 39065-95-7, name is 4-(Chlorodifluoromethoxy)aniline, A new synthetic method of this compound is introduced below., HPLC of Formula: C7H6ClF2NO

The compound 4-(chlorodifluoromethoxy)aniline (2.86 g, 14.6 mmol) was dissolved in 20 mL of DMF, and 5-bromo-6-chloronicotinic acid (3.45 g, 14.6 mmol), HATU (6.66 g, 17.52 mmol) and DIPEA (3.77 g, 29.2 mmol), stirred at room temperature for 2 hours. The reaction solution was poured into 100mL water and extracted three times with 20mL of ethyl acetate, the combined ethyl acetate and washed with saturated brine. Dry over anhydrous sodium sulfate and concentrate by filtration. Column chromatography (petroleum ether / ethyl acetate, 3/1) gave white solid powder 3.35 g. The yield was 60.3%.

The synthetic route of 39065-95-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shenzhen Tajirui Bio-pharmaceutical Co., Ltd.; Wang Yihan; Zhao Jiuyang; (35 pag.)CN109651359; (2019); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Some scientific research about 4-(Chlorodifluoromethoxy)aniline

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

To a solution of (R)-9-bromo-4-hydroxy1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyridine-7-carboxylic acid (38d, 30 mg, 0.096 mmol) in DMF (2 mL) was added HATU (54.99 mg, 0.145 mmol), DIEA (124.62 mg, 0.964 mmol, 167.95 uL) and 4-[chloro(difluoro)methoxy]aniline (1h, 28.00 mg, 0.145 mmol). The mixture was stirred at 15 C. for 16 hr. TLC (ethyl acetate_methanol=10:1, Rf=0.3) indicated a new spot was generated. LCMS showed a peak with desired MS was detected. The mixture was quenched with water (20 mL) and the mixture was extracted with ethyl acetate (30 mL*3). The combined organic layers were washed with brine (20 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude product was purified by prep-TLC (ethyl acetate_methanol=10:1, Rf=0.3) to give 38e as a yellow solid.

Application of 4-(Chlorodifluoromethoxy)aniline

To a solution of 7-bromo-6-fluoro-1-isopropyl-1H-benzo[d]imidazole-5-carboxylic acid (20f, 70 mg, 0.232 mmol, 1 eq) in DMF (2 mL) was added HATU (106.07 mg, 0.279 mmol, 1.2 eq), 4-[chloro(difluoro)methoxy]aniline (1h, 49.50 mg, 0.256 mmol, 1.1 eq) and DIEA (90.13 mg, 0.697 mmol, 121.47 uL, 3 eq). The mixture was stirred at 50 C. for 3 hr. TLC (petroleum ether:ethyl acetate=1:1) indicated 20f consumed completely. The reaction mixture was concentrated under reduced pressure. The residue was diluted with H2O (10 mL) and extracted with EtOAc (10 mL*3). The combined organic layers were washed with brine (10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give the crude product. The residue was purified by column chromatography (SiO2, petroleum ether/ethyl acetate=10/1 to 1:1). Compound 20g was obtained as a white solid. 1H NMR (400 MHz, MeOD-d4) delta 8.57 (s, 1H), 8.01 (d, J=6.4 Hz, 1H), 7.82 (d, J=8.8 Hz, 2H), 7.30 (d, J=9.3 Hz, 2H), 5.70 (td, J=6.7, 13.6 Hz, 1H), 1.67 (d, J=6.8 Hz, 6H).

Continuously updated synthesis method about 39065-95-7

The synthetic route of 39065-95-7 has been constantly updated, and we look forward to future research findings.

To a solution of 1-methyl-7-(pyrimidin-5-yl)-1H-benzo[d]imidazole-5-carboxylic acid (1g, 0.04 g, 0.157 mmol, 1 eq) and 4-(chlorodifluoromethoxy)aniline (33.50 mg, 0.173 mmol, 1.1 eq), HATU (71.79 mg, 0.189 mmol, 1.2 eq) in DMF (1 mL) at 15 C. was added DIEA (61.00 mg, 0.472 mmol, 82.21 uL, 3 eq). The mixture was stirred at 15 C. for 12 hours. LCMS showed ig was consumed completely and desired mass was detected. The mixture was concentrated, and the resulting residue was purified by prep-HPLC (FA condition, column: Luna C18 100*30 5u; mobile phase: [water (0.225% FA)-ACN]; B %: 35%-50%, 14 min) to afford the title compound 1 as a yellow solid. 1H NMR (400 MHz, MeOD-d4) delta 1N NMR (400 MHz, MeOD-d4) delta 9.31 (s, 1H), 9.06 (s, 2H), 8.45 (d, J=1.5 Hz, 1H), 8.39 (s, 1H), 7.91 (d, J=1.5 Hz, 1H), 7.84 (d, J=9.0 Hz, 2H), 7.31 (d, J=9.0 Hz, 2H), 3.60 (s, 3H).

The synthetic route of 39065-95-7 has been constantly updated, and we look forward to future research findings.

Extended knowledge of 39065-95-7

The synthetic route of 39065-95-7 has been constantly updated, and we look forward to future research findings.

Application of 39065-95-7,Some common heterocyclic compound, 39065-95-7, name is 4-(Chlorodifluoromethoxy)aniline, molecular formula is C7H6ClF2NO, 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.

A suspension of 3-bromo-4-fluoro-5-nitrobenzoic acid (24b, 150 mg, 0.568 mmol) in SOCl2 (2 mL) was stirred at 60 C. for 3 hours. The mixture was concentrated to obtain 3-bromo-4-fluoro-5-nitro-benzoyl chloride (214 mg, crude) as a white solid. To a mixture of 4-(chlorodifluoromethoxy)aniline (1h, 146.64 mg, 0.758 mmol) and pyridine (89.89 mg, 1.13 mmol, 91.72 uL) in THF (2 mL) under N2 was added 3-bromo-4-fluoro-5-nitro-benzoyl chloride (213.97 mg, 0.758 mmol). The mixture was stirred at 20 C. for 3 hours. LCMS showed the desired MS. The mixture was extracted with ethyl acetate (2 mL*3), the combined organic layers were washed with brine (5 mL*2), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by prep-TLC (SiO2, petroleum ether:ethyl acetate=1: 1, Rf=0.3). Compound 24c was obtained as a white solid.

The synthetic route of 39065-95-7 has been constantly updated, and we look forward to future research findings.

Extended knowledge of 4-(Chlorodifluoromethoxy)aniline

To a mixture of (S)-9-bromo-2-hydroxy-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyridine-7-carboxylic acid (43e, 280 mg, 899.94 umol) and HATU (376.40 mg, 989.93 umol) in DMF (3 mL) at 20 C. was added 4-(chlorodifluoromethoxy)aniline (1 h, 209.05 mg, 1.08 mmol) and DIPEA (232.62 mg, 1.80 mmol) in one portion. The mixture was stirred at 20 C. for 12 hours. LCMS showed 43e was consumed completely and one main peak with desired mass was detected. TLC (methanol:dichloromethane=10:1, Rf=0.41) indicated 43e was consumed completely and one new spot formed. The mixture was poured into EtOAc (20 mL), washed with water (5 mL*4) and brine (5 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by prep-TLC (SiO2, ethyl acetate_methanol=10:1) to give 43f as a yellow solid. 1H NMR (400 MHz, CDCl3-d) delta 10.47 (s, 1H), 8.25 (d, J=1.1 Hz, 1H), 7.99 (d, J=1.2 Hz, 1H), 7.96-7.90 (m, 2H), 7.36 (d, J=8.9 Hz, 2H), 5.37 (d, J=3.4 Hz, 1H), 4.58 (d, J=3.8 Hz, 2H), 4.38-4.30 (m, 1H), 3.22-2.96 (m, 2H), 2.04-1.99 (m, 2H).

Sources of common compounds: 39065-95-7

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, 4-(Chlorodifluoromethoxy)aniline, other downstream synthetic routes, hurry up and to see.

Synthetic Route of 39065-95-7, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 39065-95-7, name is 4-(Chlorodifluoromethoxy)aniline belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

To a reaction flask were added 6-chloro-5-bromonicotinic acid (1.17 g, 4.97 mmol), 4-(chlorodifluoromethoxy)aniline (0.8 g, 4.15 mmol), dissolved with 20 mL anhydrous DMF, 2-(7-aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU, 2.1 g, 5.39 mmol) and N,N-diisopropylethylamine (DIPEA, 534 mg, 4.15 mmol) were added, and the reaction was stirred under nitrogen protection at room temperature for 18 hours. The reaction was diluted with large amount of water, extracted with ethyl acetate for 3-4 times, the organic layers were combined, washed with brine, concentrated, purified by column chromatography, dried in vacuum to afford 1.18 g of a product, yield: 69.5%.

Reference:
Patent; Shenzhen Targetrx, Inc.; WANG, Yihan; ZHAO, Jiuyang; AL, Yixin; (55 pag.)EP3553056; (2019); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics