Category: 20188-40-3

Application of 20188-40-3, A common heterocyclic compound, 20188-40-3, name is 4-(Aminomethyl)benzamide hydrochloride, molecular formula is C8H11ClN2O, 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 ethyl 2-(bromomethyl)-6-(2-fluoro-4-(trifluoromethyl)phenoxy)benzoate (0.21 g) obtained in Reference Example 328 in ethanol (2 mL) were added 4-(aminomethyl)benzamide hydrochloride (0.11 g) and potassium carbonate (0.14 g), and the mixture was stirred at 45°C overnight. The reaction mixture was diluted with water and ethyl acetate. The organic layer was separated, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel chromatography (hexane-ethyl acetate), and the obtained solid was recrystallized from ethyl acetate-ethanol. The obtained crystals were collected by filtration and dried to give the title compound (0.055 g). MS: [M+H]+ 445.1 1H NMR (300 MHz, DMSO-d6) delta 4.42 (2H, s), 4.68 (2H, s), 7.04 (1H, t, J = 8.4 Hz), 7.15 (1H, d, J = 7.9 Hz), 7.31 (3H, d, J = 8.1 Hz), 7.46 (1H, d, J = 7.6 Hz), 7.51 (1H, d, J = 8.5 Hz), 7.62-7.69 (1H, m), 7.81-7.96 (4H, m).

The synthetic route of 20188-40-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Takeda Pharmaceutical Company Limited; SUGIMOTO, Takahiro; NAKAMURA, Minoru; SAKAMOTO, Hiroki; SUZUKI, Shinkichi; YAMADA, Masami; KAMATA, Makoto; KOJIMA, Takuto; FUJIMORI, Ikuo; SHIMOKAWA, Kenichiro; EP2921480; (2015); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Reference of 20188-40-3, Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 20188-40-3, name is 4-(Aminomethyl)benzamide hydrochloride, This compound has unique chemical properties. The synthetic route is as follows.

Example A85 Preparation of (2S,3Z)-5-{[(2R,3R,5S,6S)-6-{(2E,4E)-5-[(3R,4R,5R,7S)-7-{2-[(4- carbamoylbenzyl)amino]-2-oxoethyl}-4-hydroxy-l,6-dioxaspiro[2.5]oct-5-yl]-3-methylpenta-2,4- dien-l-yl}-2,5-dimethyltetrahydro-2H-pyran-3-yl]amino}-5-oxopent-3-en-2-yl acetate (B266). Step 1. Synthesis of (2S,32)-5- {[(2R,3R,5S,6S)-6- {(2¡ê’,4¡ê’)-5-[(3R,4R,5R,7S)-7-{2-[(4- carbamoylbenzyl)amino]-2-oxoethyl}-4-hydroxy-l,6-dioxaspiro[2.5]oct-5-yl]-3-methylpenta-2,4-dien- l-yl} -2,5-dimethyltetrahydro-2H-pyran-3-yl]amino} -5-oxopent-3-en-2-yl acetate (B266). To a solution of B1 (18.7 mg, 0.03 mmol, 1 eq.) in NN-dimethylformamide (0.5 mL) at rt was added NN- diisopropylethylamine (21.2 L, 0.12 mmol, 2 eq.) and 4-(aminomethyl)benzamide hydrochloride salt (11.2 mg, 0.06 mmol, 2 eq.), and the reaction was stirred for 1 h. The reaction was purified by by reverse phase chromatography (Method A) to give B266 as a white solid. Yield: 15.4 mg, 0.023 mmol, 77percent. LCMS (Protocol D): m/z 668.37 [M+Na]+, retention time = 0.71 minutes. lB NMR (500 MHz, DMSO-d6) delta 8.50-8.43 (m, 1 H), 7.88 (s, 1 H), 7.82-7.74 (m, 3 H), 7.33-7.25 (m, 3 H), 6.41-6.27 (m, 2 H), 6.10 (d, J= 11.6 Hz, 1 H), 5.87 (dd, J= 11.6 and 7.5 Hz, 1 H), 5.62 (dd, J= 15.8 and 5.5 Hz, 1 H), 5.50-5.43 (m, 1 H), 5.04 (d, J= 5.4 Hz, 1 H), 4.43-4.20 (m, 3 H), 3.68-3.59 (m, 2 H), 3.53-3.45 (m, 1 H), 3.29-3.23 (m, 1 H), 2.78 (d, J= 5.3 Hz, 1 H), 2.68-2.56 (m, 2 H), 2.35-2.13 (m, 3 H), 1.98 (s, 3 H), 1.90-1.72 (m, 4 H), 1.70 (s, 3 H), 1.66-1.58 (m, 1 H), 1.57-1.49 (m, 1 H), 1.25 (d, J= 6.5 Hz, 3 H), 1.04 (d, J= 6.2 Hz, 3 H) , 0.93 (d, J= 7.3 Hz, 3 H).

The chemical industry reduces the impact on the environment during synthesis 4-(Aminomethyl)benzamide hydrochloride. I believe this compound will play a more active role in future production and life.

Reference:
Patent; PFIZER INC.; DIRICO, Kenneth John; EUSTAQUIO, Alessandra S.; GREEN, Michael Eric; HE, Haiyin; HE, Min; KOEHN, Frank Erich; O’DONNELL, Christopher John; PUTHENVEETIL, Sujiet; RATNAYAKE, Anokha Sayani; SUBRAMANYAM, Chakrapani; TESKE, Jesse Alexander; YANG, Hui Yu; WO2014/68443; (2014); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Application of 20188-40-3,Some common heterocyclic compound, 20188-40-3, name is 4-(Aminomethyl)benzamide hydrochloride, molecular formula is C8H11ClN2O, 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.

Ethyl 2-(2-fluoro-4-propylphenoxy)-4-formylnicotinate (0.13 g) obtained in Reference Example 319 was dissolved in methanol (3 mL), 4-(aminomethyl)benzamide hydrochloride (0.082 g), acetic acid (0.024 g) and triethylamine (0.061 g) were added, and the mixture was stirred at room temperature for 1 hr. To the reaction mixture was added sodium tetrahydroborate (0.15 g), and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with water and ethyl acetate. The organic layer was separated, washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by NH silica gel chromatography (hexane-ethyl acetate), and recrystallized from ethyl acetate-ethanol to give the title compound (0.079 g). MS: [M+H]+ 420.2 1H NMR (300 MHz, DMSO-d6) delta0.93 (3H, t, J = 7.3 Hz), 1.63 (2H, sxt, J = 7.4 Hz), 2.56-2.65 (2H, m), 4.48 (2H, s), 4.76 (2H, s), 7.02-7.14 (1H, m), 7.16-7.28 (2H, m), 7.34 (2H, d, J = 5.1 Hz), 7.38 (2H, d, J = 8.3 Hz), 7.87 (2H, d, J = 8.3 Hz), 7.94 (1H, brs), 8.20 (1H, d, J = 5.1 Hz).

The synthetic route of 20188-40-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Takeda Pharmaceutical Company Limited; SUGIMOTO, Takahiro; NAKAMURA, Minoru; SAKAMOTO, Hiroki; SUZUKI, Shinkichi; YAMADA, Masami; KAMATA, Makoto; KOJIMA, Takuto; FUJIMORI, Ikuo; SHIMOKAWA, Kenichiro; EP2921480; (2015); A1;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics