Category: 1914-02-9

Reference of 1914-02-9, The chemical industry reduces the impact on the environment during synthesis 1914-02-9, name is 3,3-Dimethylindoline, I believe this compound will play a more active role in future production and life.

To a solution of l-((tert-butoxycarbonyl)amino)cyclopropanecarboxylic acid (155 mg, 0.770 mmol) in 7 mL DMF, triethylamine (130 mu,, 0.933 mmol) and HATU (325 mg, 0.855 mmol) were added. After stirring at room temperature for 5 min, 3,3-dimethylindoline (105 mg, 0.713 mmol) was added. After stirring at room temperature for overnight, the mixture was extracted with AcOEt and brine. Organic phase was dried over MgS04, filtered, and concentrated. The residue was purified by silica gel column chromatography to give tert-butyl (l-(3,3-dimethylindoline-l- carbonyl)cyclopropyl)carbamate (215 mg) as a white solid. LCMS m/z = 331.2 [M+l]+; NMR (400 MHz, CDC13) delta ppm 1.02-1.15 (m, 2H), 1.33 (s, 6H), 1.40 (s, 9H), 1.54-1.57 (m, 2H), 4.03 (s, 2H), 7.03-7.05 (m, 1H), 7.13-7.15 (m, 1H), 7.18-7.22 (m, 1H), 7.92-7.93 (m, 1H).

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, 3,3-Dimethylindoline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ARENA PHARMACEUTICALS, INC.; SEMPLE, Graeme; BEHAN, Dominic P.; FEICHTINGER, Konrad; GLICKLICH, Alan; GROTTICK, Andrew J.; KAM, Maria Matilde Sanchez; KASEM, Michelle; LEHMANN, Juerg; REN, Albert S.; SCHRADER, Thomas O.; SHANAHAN, William R.; WONG, Amy Siu-Ting; ZHU, Xiuwen; WO2015/66344; (2015); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Related Products of 1914-02-9, 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. 1914-02-9 name is 3,3-Dimethylindoline, 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.

A mixture of 3,3-dimethylindoline (105 mg, 0.713 mmol), ethyl 2-bromo-2-cyclopropylacetate (297 muL, 2.143 mmol), and potassium carbonate (300 mg, 2.171 mmol) in 2 mL CH3CN was stirred at 100C (oil bath) for 16 h. The mixture was extracted with 2 M HC1 and CH2C12. Organic phases were concentrated and residue was purified by preparative HPLC. Fractions containing product were partly concentrated and the residue was extracted with 1 M NaHC03and CH2C12. Organic phases were dried over MgS04, filtered, and concentrate to give ethyl 2-cyclopropyl-2-(3,3-dimethylindolin-l-yl)acetate (162 mg) as a brownish oil. LCMS m/z = 274.4 [M+l]+; NMR (400 MHz, CDC13) delta ppm 0.37-0.43 (m, 1H), 0.52-0.58 (m, 1H), 0.61-0.73 (m, 2H), 1.20 (t, J = 7.1 Hz, 3H), 1.26-1.34 (m, 7H), 3.33 (d, J = 9.4 Hz, 1H), 3.49 (d, J = 8.4 Hz, 1H), 3.61 (d, J = 8.4 Hz, 1H), 4.13 (q, J = 7.1 Hz, 2H), 6.30 (dd, J1= 7.5 Hz, J2= 0.8 Hz, 1H), 6.63-6.67 (m, 1H), 6.98-7.02 (m, 2H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3,3-Dimethylindoline, and friends who are interested can also refer to it.

Reference:
Patent; ARENA PHARMACEUTICALS, INC.; SEMPLE, Graeme; BEHAN, Dominic P.; FEICHTINGER, Konrad; GLICKLICH, Alan; GROTTICK, Andrew J.; KAM, Maria Matilde Sanchez; KASEM, Michelle; LEHMANN, Juerg; REN, Albert S.; SCHRADER, Thomas O.; SHANAHAN, William R.; WONG, Amy Siu-Ting; ZHU, Xiuwen; WO2015/66344; (2015); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

1914-02-9, A common compound: 1914-02-9, name is 3,3-Dimethylindoline, belongs to indolines-derivatives compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

Step 4. 3,3-dimethyl-2,3-dihydro-1 /-/-indole-6-sulfonic acidA mixture of 3, 3-dimethyl-2,3-dihydro-1 /-/-indole (16.0 g, 109 mmol) in fuming sulphuric acid (60 mL) was stirred at rt for 45 min. The reaction was then heated to 135 C for 1 h. After cooling the solution was poured into ice water, cooled to -50 C and allowed to stand for 2 h. The resultant precipitate was collected by filtration to give 3,3- dimethyl-2,3-dihydro-1 H-indole-6-sulfonic acid (7 g, 28 %). MS (m/z) 228.0 (M+H)+. 1H NMR (400 MHz, DMSO-d6) delta ppm 1 .31 (s, 6 H) 3.52 (s, 2 H) 7.40 (d, J=7.94 Hz, 1 H) 7.58 (s, 1 H) 7.64 (dd, J=7.83, 1 .43 Hz, 1 H)

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, 3,3-Dimethylindoline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; GLAXOSMITHKLINE LLC; KALLANDER, Lara, S.; LAWHORN, Brian, Griffin; PHILIP, Joanne; ZHAO, Yongdong; WO2011/88027; (2011); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Some common heterocyclic compound, 1914-02-9, name is 3,3-Dimethylindoline, molecular formula is C10H13N, 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. 1914-02-9

22d. 3,3-dimethyl-1-(3-nitropyridin-2-yl)indoline The product of 22c (200 mg, 1.35 mmol) and 2-fluoro-3-nitropyridine (0.3 mL) were pre-stirred in a conical microwave container. The mixture was heated at 200 C. under microwave with stirring at high absorption for 10 min. The cooled mixture was dissolved in EtOAc, washed with H2O, brine, dried over MgSO4, filtered, and concentrated to dryness. The residue was purified by flash column chromatography (silica gel, hexanes/EtOAc) to give pure 22d (220 mg, yield: 60.4%). LC-MS ESI 270 (M+H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1914-02-9, its application will become more common.

Reference:
Patent; Tuerdi, Huji; Chao, Hannguang J.; Qiao, Jennifer X.; Wang, Tammy C.; Gungor, Timur; US2005/261244; (2005); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

1914-02-9, A common heterocyclic compound, 1914-02-9, name is 3,3-Dimethylindoline, molecular formula is C10H13N, 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 3- (chlorosulfonyl) benzoic acid (456 mg, 2.07 mmol, Aldrich) in CH2Cl2 (15 [ML)] was added DMF (15 [UL)] followed by oxalyl chloride (270 [; J, L,] 3.10 mmol). After stirring for 1.5 hours, the solvent and excess oxalyl chloride were removed by rotary evaporation. The residue was dissolved in toluene (15 mL), and [METHYL 2-AMINO-5-CYANOBENZOATE (370 MG,] 2.10 mmol) was added. The mixture was heated in a [105 C] oil bath for 2 hours, and the toluene was then removed by rotary evaporation. The residue was dissolved in [CH2CLZ] (6 mL), and a mixture of 3,3- [DIMETHYLINDOLINE,] descrinbed by Kucerovy et al. in Synth. Commun. 1992, 22 (5), 729- 733, (342 mg, 2.32 mmol) and triethylamine (600 [-LL,] 4.31 mmol) in [CH2C12] (6 [ML)] was added. This mixture was stirred overnight and then added to a separatory funnel with 100 mL of [CH2C12.] This solution was washed with 2 X 100 [ML] of 1 M aqueous HC1 and 100 [ML] of brine. The [CH2CK WAS] evaporated in the presence of silica gel, and the product was purified by chromatography using a Biotage Flash 40 M silica cartridge with a gradient from [CHUCK] to [1 % ETOAC] in [CH2C12 AS] eluent. Yield was 728 mg of white solid as the methyl ester. The methyl ester was hydrolyzed according to method D yielding 292 mg of white [SOLID. 1H] NMR (400 MHz, DMSO-d6) [8 12.] 57 (s, [1] H), 8. [80] (d, [J=] 8.7 Hz, [1 H),] 8.41-8. 44 (m, 2 H), 8.24 (d, [J=] 7.9 Hz, 1 H), 8.09- 8.14 (m, 2 H), 7.83 (t, J= 7.9 Hz, [1] H), 7.55 (d, J= 8.1 Hz, 1 [H),] 7.24 (t, J= 7.7 Hz, 1 H), 7.18 (d, [J=] 7.7 Hz, [1] H), 7.02 (t, [J=] 7.5 Hz, [1 H),] 3.73 (s, 2 H), 1. [08] (s, 6 H).

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

Reference:
Patent; PHARMACIA & UPJOHN COMPANY; WO2004/18414; (2004); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

Adding a certain compound to certain chemical reactions, such as: 1914-02-9, name is 3,3-Dimethylindoline, belongs to indolines-derivatives compound, 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 1914-02-9, 1914-02-9

To a solution of (R)-2-((tert-butoxycarbonyl)amino)propanoic acid (141 mg, 0.745 mmol) in 7 mL DMF, triethylamine (125 mu,, 0.897 mmol) and HATU (322 mg, 0.847 mmol) were added. After stirring at room temperature for 5 min, 3,3-dimethylindoline (101 mg, 0.686 mmol) was added. After stirring at room temperature for overnight, the mixture was extracted with AcOEt and brine. The organic phase was dried over MgS04, filtered, and concentrated. The residue was purified by silica gel column chromatography to give (R)-tert-butyl (l-(3,3-dimethylindolin-l-yl)-l-oxopropan-2- yl)carbamate (205 mg) as a white solid. LCMS m/z = 319.4 [M+l]+; NMR (400 MHz, CDC13) delta ppm 1.358 (s, 3H), 1.364 (s, 3H), 1.40 (d, J = 6.8 Hz, 3H), 1.45 (s, 9H), 3.78 (d, J = 10.0 Hz, 1H), 4.00 (d, J = 10.0 Hz, 1H), 4.54-4.61 (m, 1H), 5.46 (d, J = 8.5, 1H), 7.07-7.10 (m, 1H), 7.15-7.16 (m, 1H), 7.20-7.24 (m, 1H), 8.17 (d, J = 8.1 Hz, 1H).

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, 3,3-Dimethylindoline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ARENA PHARMACEUTICALS, INC.; SEMPLE, Graeme; BEHAN, Dominic P.; FEICHTINGER, Konrad; GLICKLICH, Alan; GROTTICK, Andrew J.; KAM, Maria Matilde Sanchez; KASEM, Michelle; LEHMANN, Juerg; REN, Albert S.; SCHRADER, Thomas O.; SHANAHAN, William R.; WONG, Amy Siu-Ting; ZHU, Xiuwen; WO2015/66344; (2015); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 1914-02-9 as follows. 1914-02-9

Intermediate 66 (300mg, 1.2mmol), 3,3-dimethylindoline (182mg, 1.2mmol) and propan-2-ol (3m1) were sealed in a vial and heated at 70C for 4 hours. The mixture was cooled, at which point a precipitate formed. This was collected and dried via vacuum filtration to afford ethyl 7-(3,3-dimethylindolin-1 -yl)thiazolo[5,4-d]pyrimidine-2- carboxylate, as a yellow solid (322mg, 74%); 1H NMR (400 MHz, CHLOROFORM-d) 5ppm 1.48 (m, 9 H), 4.56 (q, .1=7.33 Hz, 2 H), 4.80 (s, 2 H), 7.31 -7.41 (m, 3 H), 8.65 (d, J-7.78 Hz, I H), 8.75 (s, I H); LC-MS (ESI): (MW)355.0

According to the analysis of related databases, 1914-02-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MEDICAL RESEARCH COUNCIL TECHNOLOGY; WINTER-HOLT, Jon James; MCIVER, Edward Giles; AMBLER, Martin; LEWIS, Stephen; OSBORNE, Joanne; WEBB-SMITH, Kayleigh; (257 pag.)WO2017/85484; (2017); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

1914-02-9, A common heterocyclic compound, 1914-02-9, name is 3,3-Dimethylindoline, molecular formula is C10H13N, 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.

Example 37 1. Synthesis of intermediate 037-2 The intermediate 001-5 (2.22 g, 14.9 mmol), anhydrous THF (25 mL), 037-1 (1.5 g, 10.2 mmol) and DIPEA (2.58 g, 20.0 mmol) were added into a 100 mL single-necked flask sequentially, and then the reaction was heated to 75C and maintained under stirring for 2.5 h. The reaction was cooled to room temperature, and the reaction mixture was subjected to rotary evaporation, and the crude product was purified through silica gel column chromatography (eluent: EA:PE = 1:15) to give 1.5 g of the intermediate 037-2 (57%) as a white solid. LCMS: 260.1.

The synthetic route of 1914-02-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shanghai Shaletech Technology Co., Ltd.; JIANG, Yueheng; (143 pag.)EP3216786; (2017); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem

1914-02-9, 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. 1914-02-9 name is 3,3-Dimethylindoline, 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.

The product is prepared according to the procedure described in example 5, using 177 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate, 236 mg of 3,3-dimethylindoline (which can be prepared according to T. W. Ramsay et al., Synth. Commun. 1995, 25, 4029) and 169 mg of N-[3-(dimethylamino)propyl]-N?-ethylcarbodiimide hydrochloride in a mixture of 0.11 ml of pyridine and 5 ml of N,N-dimethylformamide. The reaction mixture is stirred for 15 h at ambient temperature and then concentrated to dryness under reduced pressure. 40 ml of water are added to the residue and triturated with a spatula at ambient temperature. The precipitate formed is filtered off, and then solubilized with a dichloromethanemethanol mixture and dried. After concentration to dryness under reduced pressure, the crude product is purified by chromatography on a 30 g silica (0.02-0.045 mm) column, eluent: 90/10 v/v dichloromethanemethanol. After the various fractions have been evaporated, the pink solid residue is triturated from 10 ml of diisopropyl ether, filtered off, and then dried under a bell jar (1h40 C./20 mbar). 134 mg of 2-[2-(3,3-dimethyl-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one are thus obtained in the form of a pink solid

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3,3-Dimethylindoline, and friends who are interested can also refer to it.

Reference:
Patent; Sanofi; Cali, Jean – Christophe; Sertar, Victor; Array, Frank; Carlson, Carl Andreas; Shio, Laulan; Thompson, Fabienne; (178 pag.)JP5680638; (2015); B2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem