Category: 718632-46-3

These common heterocyclic compound, 718632-46-3, name is 5-tert-Butyl 2-ethyl 3-amino-6,6-dimethylpyrrolo[3,4-c]pyrazole-2,5(4H,6H)-dicarboxylate, 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. Quality Control of 5-tert-Butyl 2-ethyl 3-amino-6,6-dimethylpyrrolo[3,4-c]pyrazole-2,5(4H,6H)-dicarboxylate

To a solution of 9.70 g (61.3 mmol) of 1-(trimeth- ylsilyl)cyclopropanecarboxylic acid [synthesized according to the method described in J. Org. Chem., 1982(47) 5, 893-895] in 120 ml of dehydrated dichloromethane, 6.60 ml (76.9 mmol) of oxalyl chloride and 0.25 ml (3.2 mmol) of dehydrated DMF were added in this order at 00 C. in a nitrogen atmosphere and reacted at 00 C. for 2.5 hours with stirring. After completion of the reaction, the reaction solution was concentrated under reduced pressure and dried under reduced pressure. A solution of the obtained concentration residue in 30 ml of dehydrated dichloromethane was added to a solution of 19.0 ml (109 mmol) of DIPEA and 9.94 g (30.6 mmol) of 5-tert-butyl 2-ethyl 3-amino-6,6- dimethylpyrrolo[3,4-c]pyrazole-2,5(4H,6H)-dicarboxylate[synthesized according to the method described in Journal of Medicinal Chemistry 2012, 55 (10), 4728-4739] in 170 ml of dehydrated dichioromethane at 00 C. in a nitrogen atmosphere and reacted at 00 C. for 24 hours with stirring. After completion of the reaction, a saturated aqueous solution of sodium bicarbonate was added to the reaction solution and stirred, followed by extraction once with dichloromethane and twice with ethyl acetate. The whole organic layer thus obtained was dried over anhydrous magnesium sulfate, then filtered, and concentrated under reduced pressure. The obtained concentration residue was subjected to preparative column chromatography (apparatus 2, silica gel, elution solvent: n-hexane:ethyl acetate=90: 10-70:30 (V/V)), and a fraction containing 5-tert-butyl 2-ethyl 6,6- dimethyl-3-[1 -(trimethylsilyl)cyclopropanecarboxamido]pyrrolo[3,4-c]pyrazole-2,5(4H,6H)-dicarboxylate was concentrated under reduced pressure. The concentration residue of the fraction containing impurities was subjected again to preparative column chromatography (apparatus 2, silica gel, elution solvent: n-hexane: ethyl acetate=90: 1 0-75 :25 (V/V)), combined with the preliminarily obtained fraction, concentrated under reduced pressure, and dried under reduced pressure.

The synthetic route of 5-tert-Butyl 2-ethyl 3-amino-6,6-dimethylpyrrolo[3,4-c]pyrazole-2,5(4H,6H)-dicarboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; UBE INDUSTRIES, LTD.; IWASE, Noriaki; AGA, Yasuhiro; USHIYAMA, Shigeru; KONO, Shigeyuki; SUNAMOTO, Hidetoshi; MATSUSHITA, Takashi; OGI, Sayaka; UMEZAKI, Satoshi; KOJIMA, Masahiro; ONUMA, Kazuhiro; SHIRAISHI, Yusuke; OKUDO, Makoto; KIMURA, Tomio; (165 pag.)US2018/186818; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 718632-46-3, 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. 718632-46-3, name is 5-tert-Butyl 2-ethyl 3-amino-6,6-dimethylpyrrolo[3,4-c]pyrazole-2,5(4H,6H)-dicarboxylate, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of 9.70 g (61.3 mmol) of 1-(trimethylsilyl)cyclopropanecarboxylic acid [synthesized according to the method described in J. Org. Chem., 1982 (47) 5, 893-895] in 120 ml of dehydrated dichloromethane, 6.60 ml (76.9 mmol) of oxalyl chloride and 0.25 ml (3.2 mmol) of dehydrated DMF were added in this order at 0C in a nitrogen atmosphere and then stirred for 2.5 hours with the temperature unchanged. After the completion of the reaction, the reaction solution was concentrated under reduced pressure and dried under reduced pressure to obtain a concentration residue. To a solution of 19.0 ml (109 mmol) of DIPEA and 9.94 g (30.6 mmol) of 5-tert-butyl 2-ethyl 3-amino-6,6-dimethylpyrrolo[3,4-c]pyrazole-2,5(4H,6H)-dicarboxylate [synthesized according to the method described in Journal of Medicinal Chemistry 2012, 55 (10), 4728-4739] in 170 ml of dehydrated dichloromethane, a solution of the obtained concentration residue in 30 ml of dehydrated dichloromethane was added at 0C in a nitrogen atmosphere and then stirred for 24 hours with the temperature unchanged. After the completion of the reaction, a saturated aqueous solution of sodium bicarbonate was added to the reaction solution and stirred, followed by extraction with dichloromethane once and ethyl acetate twice. All of the obtained organic layers were dried over anhydrous magnesium sulfate, then filtered, and concentrated under reduced pressure. The obtained concentration residue was subjected to silica gel column chromatography (elution solvent: n-hexane:ethyl acetate = 90:10 to 70:30 (V/V)), and a fraction containing the compound of interest was concentrated under reduced pressure. A concentration residue of a fraction containing impurities was subjected again to silica gel column chromatography (elution solvent: n-hexane:ethyl acetate = 90:10 to 75:25 (V/V)), combined with the purified form obtained above, concentrated under reduced pressure, and dried under reduced pressure to obtain 10.63 g of a concentration residue. To a solution of the obtained concentration residue in 100 ml of ethyl acetate, 60.0 ml (240 mmol) of 4 N hydrogen chloride/ethyl acetate was added at room temperature in a nitrogen atmosphere and then stirred for 5 hours with the temperature unchanged. After the completion of the reaction, the reaction solution was concentrated under reduced pressure. The obtained concentration residue was suspended in diisopropyl ether, and the suspension was stirred at room temperature. Insoluble matter was collected by filtration, and the obtained solid was washed with diisopropyl ether. The obtained solid was dissolved in water, and then, a saturated aqueous solution of sodium bicarbonate and dichloromethane were added and stirred at room temperature for 5 minutes. After separation into an aqueous layer and an organic layer, the aqueous layer was subjected to extraction with dichloromethane twice. All of the organic layers were washed with a saturated aqueous solution of sodium chloride, then dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and dried under reduced pressure to obtain 8.27 g of the title compound (yield: 73% [2 steps]) as a light orange solid. Mass spectrum (DUIS, m/z): 365 [M+1]+. 1H-NMR spectrum (400 MHz, CDCl3) delta: 10.02 (s, 1H), 4.53 (q, J = 7.2 Hz, 2H), 4.16 (s, 2H), 1.50 – 1.43 (m, 9H), 1.14 – 1.08 (m, 2H), 0.84 – 0.77 (m, 2H), 0.12 (s, 9H).

The chemical industry reduces the impact on the environment during synthesis 5-tert-Butyl 2-ethyl 3-amino-6,6-dimethylpyrrolo[3,4-c]pyrazole-2,5(4H,6H)-dicarboxylate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Ube Industries, Ltd.; AGA, Yasuhiro; USHIYAMA, Shigeru; IWASE, Noriaki; KONO, Shigeyuki; SUNAMOTO, Hidetoshi; MATSUSHITA, Takashi; OGI, Sayaka; TANAKA, Masayuki; MATOYAMA, Masaaki; UMEZAKI, Satoshi; SHIRAISHI, Yusuke; ONUMA, Kazuhiro; KOJIMA, Masahiro; NISHIYAMA, Hayato; KIMURA, Tomio; (481 pag.)EP3214086; (2017); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

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. 718632-46-3, name is 5-tert-Butyl 2-ethyl 3-amino-6,6-dimethylpyrrolo[3,4-c]pyrazole-2,5(4H,6H)-dicarboxylate, A new synthetic method of this compound is introduced below., Quality Control of 5-tert-Butyl 2-ethyl 3-amino-6,6-dimethylpyrrolo[3,4-c]pyrazole-2,5(4H,6H)-dicarboxylate

Example 1; 6,6-Dimethyl-3-[4-(4-methyl-piperazin-l-yl)-benzoylamino]-4,6-dihydro-lH- pyrrolo[3,4-c]pyrazole-2,5-dicarboxylic acid 5-tert-butyl ester 2-ethyl ester [Formula (IV), R = 4-(4-methyl-piperazin)-phenyl]; To a solution of 3-Amino-6,6-dimethyl-4H,6H-pyrrolo[3,4-c]pyrazole-2,5- dicarboxylic acid 5-tert-butyl ester 2-ethyl ester (2.50 g, 7.70 mmol) prepared as reported in WO2004/056827, N,N-diispropylethylamine (14.6ml, 33.6mmol) in anhydrous Dioxane (100 ml), 4-(4-Methyl-piperazin-l-yl)-benzoyl chloride (0.24 g ,1.00 mmol) was added. The reaction was heated to reflux and stirred for 6h. The solvent was removed under vacuum, the residue dissolved in CH2Cl2 (150 mL) and washed with brine (I X 10OmL). The organic phase was dried over sodium sulphate, the solvent evaporated in vacuo and the residue purified by flash chromatography (Acetone/DCM 80/20) affording 2.1O g (yield 52%) of the title compound. ESI MS: m/z 527 (MH+); 1H NMR (400 MHz, DMSO-d6): delta 10.69 (s, IH), 7.76 (m, 2H), 7.09 (m, 2H), 4.55 (d, 2H, J = 9.8 Hz), 4.48 (q, 2H, J = 7.1 Hz), 3.34 (m, 4H), 2.52 (m, 4H), 2.27 (s, 3H ), 1.64 (s, 3H ), 1.62 (s, 3H ), 1.47 (s, 9H), 1.38 (t, 3H, J= 7.1 Hz).

The synthetic route of 718632-46-3 has been constantly updated, and we look forward to future research findings.

Reference of 718632-46-3, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 718632-46-3 name is 5-tert-Butyl 2-ethyl 3-amino-6,6-dimethylpyrrolo[3,4-c]pyrazole-2,5(4H,6H)-dicarboxylate, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

To a suspension of 2-(l,3-dioxo-l,3-dihydro-isoindol-2-ylmethyl)-benzoic acid (1.35 g, 4.8 mmol) in dry dichloromethane (30 mL), at 0 C, under stirring, was added oxalyl chloride (2.1 mL, 24 mmol) and dry N,N-dimethylformamide (35 microL). The mixture was allowed to warm to room temperature, stirred for 1.5 hours then evaporated to dryness. The residue was diluted with dry toluene and evaporated again. The crude acyl chloride thus obtained (yellow solid) was dissolved in dry tetrahydrofuran (20 mL) and treated with N,N-diisopropylethylamine (2.5 mL, 15 mmol) and with a solution of 3- amino-6,6-dimethyl-4H,6H-pyrrolo[3,4-c]pyrazole-2,5-dicarboxylic acid 5-tert-butyl ester 2-ethyl ester (1.3 g, 4 mmol) in 15 mL of dry tetrahydrofuran. The mixture was stirred at room temperature for 2 days then evaporated to dryness. The residue was dissolved in dichloromethane, washed with IN HCl, water, saturated solution of NaHCC>3, brine, dried over sodium sulfate and evaporated to dryness. The crude was purified by flash chromatography on silica gel using dichloromethane/methanol 98.5:1.5 as the eluant affording the title compound as white solid (1.5 g).IH-NMR (400 MHz), delta (ppm, DMSOtZ6): 10.63 (bs, IH), 7.91-7.83 (m, 4H), 7.71 (m, IH), 7.58-7.46 (m, 2H), 7.37 (m, IH), 5.07 (s, 2H), 4.53 (bs, 2H), 4.43 (m, 2H), 1.63 (bs, 6H), 1.50 (s, 9H), 1.37 (m, 3H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-tert-Butyl 2-ethyl 3-amino-6,6-dimethylpyrrolo[3,4-c]pyrazole-2,5(4H,6H)-dicarboxylate, and friends who are interested can also refer to it.

These common heterocyclic compound, 718632-46-3, name is 5-tert-Butyl 2-ethyl 3-amino-6,6-dimethylpyrrolo[3,4-c]pyrazole-2,5(4H,6H)-dicarboxylate, 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. Recommanded Product: 5-tert-Butyl 2-ethyl 3-amino-6,6-dimethylpyrrolo[3,4-c]pyrazole-2,5(4H,6H)-dicarboxylate

Example 5; Preparation of 6,6-dimethyi-3-[4-(4-methyl-piperazin-1-yl)-2-nitro-benzoylamino]- 4H,6H-pyrrolo|;3,4-c]pyrazole-2,5-d.carboxylic acid 5-tert-butyl ester 2-thetathyl ester; 4-(4-rnethyip1perazin-1-yl)-2-nitro-ben;-oic acid (15 g, 49,7 mmol) in dry tetrahydrofuran (100 mL) was stirred with thionyl chloride (5 eq ., 18,1 mL, 2487 mmol) and a few drops of N,N-dimethyiformamide at 8QC for about 14 hours . After removal of the solvent under vacuum, the crude material was added portion-wise to a solution of 3-amino-6,6- dimethy.-4H,6H-pyrro.o[3,4~c]pyrazo.e-2,5-d.carboxytic acid 5-tert-butyl ester 2-ethyl ester (16 t g, 49 7 mmol) and IM.N-diethyiisopropylatnine (5 eq , 43 4 mL, 248 7 mmol} in 1 ,4- dioxane (200 mL) maintained under magnetic stirring at 80C The reaction mixture was stirred for about 6 hours at 80C After removal of the solvent, the crude material was diluted with dichloromethane (200 mL), washed with saturated sodium hydrogen carbonate solution (200 mL), dried over sodium sulphate, evaporated to dryness and purified by flash chromatography on sittca gel using acetone as the efuant. The titfe compound was obtained as light yellow powder (13 5 g, 47% yield). 1 H-NMR (400 MHz), 3. (ppm, DMSOd6): 10 70, 10 67{s, 1 H)1 7 68, 7 66 (d, J1 =8 78Hz, 1 H), 7 48(bs, I H), 7.30 (dd, J 1=8 78 Hz, J2=2.56 Hz, 1 H)1 4 47-4.39 (m, 4H), 3,41 (m, 4H), 2.52 (m, 4H), 2 27 (s, 3H), 1,63, 1 62 (s, 6H), 1.49, 1 46 (s, 9H)1 137, 1 36 (t, J=7 07 Hz1 3H); mixture of rotamers

The synthetic route of 5-tert-Butyl 2-ethyl 3-amino-6,6-dimethylpyrrolo[3,4-c]pyrazole-2,5(4H,6H)-dicarboxylate has been constantly updated, and we look forward to future research findings.