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[ CAS No. 141645-23-0 ] {[proInfo.proName]}

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Chemical Structure| 141645-23-0
Chemical Structure| 141645-23-0
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Product Details of [ 141645-23-0 ]

CAS No. :141645-23-0 MDL No. :MFCD18072491
Formula : C30H40N2O5 Boiling Point : -
Linear Structure Formula :- InChI Key :YIYARJKYRBMMJG-UHFFFAOYSA-N
M.W : 508.65 Pubchem ID :10209258
Synonyms :

Calculated chemistry of [ 141645-23-0 ]

Physicochemical Properties

Num. heavy atoms : 37
Num. arom. heavy atoms : 15
Fraction Csp3 : 0.5
Num. rotatable bonds : 17
Num. H-bond acceptors : 6.0
Num. H-bond donors : 0.0
Molar Refractivity : 151.76
TPSA : 88.5 Ų

Pharmacokinetics

GI absorption : Low
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -3.65 cm/s

Lipophilicity

Log Po/w (iLOGP) : 4.78
Log Po/w (XLOGP3) : 8.1
Log Po/w (WLOGP) : 7.59
Log Po/w (MLOGP) : 3.14
Log Po/w (SILICOS-IT) : 6.24
Consensus Log Po/w : 5.97

Druglikeness

Lipinski : 1.0
Ghose : None
Veber : 1.0
Egan : 1.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -7.27
Solubility : 0.000027 mg/ml ; 0.0000000531 mol/l
Class : Poorly soluble
Log S (Ali) : -9.82
Solubility : 0.0000000779 mg/ml ; 0.0000000002 mol/l
Class : Poorly soluble
Log S (SILICOS-IT) : -10.04
Solubility : 0.0000000465 mg/ml ; 0.0000000001 mol/l
Class : Insoluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 3.0
Synthetic accessibility : 4.49

Safety of [ 141645-23-0 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 141645-23-0 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 141645-23-0 ]

[ 141645-23-0 ] Synthesis Path-Downstream   1~50

  • 1
  • [ 141645-23-0 ]
  • [ 141644-91-9 ]
YieldReaction ConditionsOperation in experiment
98.4% With hydrogen In ethanol for 0.333333h; 6.A. Dronedarone Hydrochloride [0106] A. 5-Amino-2-butyl-3-(4-[3-(dibutylamino)propoxy]benzoyl)benzofuran [0107] A medium formed of 20.4 g (0.04 mol) of 2-butyl-3-(4-[3-(dibutylamino)propoxy]benzoyl)-5-nitrobenzofuran, prepared as described in example 5, 200 ml of ethanol and 0.6 g of platinum oxide is stirred in a hydrogenation device under a pressure of 3.4 atmospheres (3.44*105 Pa) of hydrogen. When the pressure reaches 2.7 atm (2.73*105 Pa), the reaction is terminated, which requires aproximately 20 minutes. [0108] In this way, 5-amino-2-butyl-3-(4-[3-(dibutylamino)propoxy]benzoylbenzofuran is obtained. [0109] Yield: 98.4%. [0110] Purity (HPLC): 95.28%.
98% With hydrogen In methanol at 45 - 50℃; 3 Preparation of 5-amino-3-[4-(3-di-n-butylamino-propoxy)benzoyl]-2-n-butyl benzofuran: Example 3 Preparation of 5-amino-3-[4-(3-di-n-butylamino-propoxy)benzoyl]-2-n-butyl benzofuran: 2-n-butyl-3-[4-(3-di-n-butylamino-propoxy)benzoyl]-5-nitro benzofuran (155 gm, 0.31 mol) in methanol (3.1 lit) was subjected to hydrogenation in presence of Raney nickel (31 gm) in a hydrogenation apparatus under pressure of about 5kg/cm2 of hydrogen and temperature of 45-50°C for 3-4 hours. The completion of reaction was monitored by TLC. The reaction mixture was filtered through hyflo bed and the residue was washed with methanol. The filtrate was concentrated to get 143 gm of titled product. Yield: 98%
98% With hydrogen In methanol at 20℃; 2 2-n-butyl-3-[4-(3-di-n-butylamino-propoxy)benzoyl]-5-nitro benzofuran (155 gm, 0.31 mol) in methanol (6.2 lit) was subjected to hydrogenation in presence of Raney nickel (31 gm) in a hydrogenation apparatus under pressure of about 5 kg/cm2 of hydrogen at room temperature for 3-4 hours. The completion of reaction was monitored by TLC. The reaction mixture was then filtered through hyflo bed and washed with methanol. The filtrate was concentrated to obtain 143 gm of titled product as an oil. Yield: 98%.
96.8% With hydrogen In ethanol at 30℃; for 6h; Autoclave; 2.1 Example 2.1. Preparation of I (crude):In 5.0 liter autoclave charged 2-n-butyl-3-[4-(3-di-n-butylamino- propoxy)benzoyl]-5-nitrobenzofuran (100.0 g) (196.85 mmols), ethanol (1000.0 ml) and 5% Pd/C (10.0 g) (50 % moisture). Hydrogen pressure was applied up to 5.0 Kg/cm at 30.0°C and stirred the reaction mass for 6 hours. At the end of this time the reaction mass was filtered through hyflo bed. Filtrate was concentrated to give reddish yellow oil (91.0 g).Molar yield: 96.80%HPLC purity: 95.08%
96.8% With hydrogen In ethanol at 30℃; for 6h; Autoclave; 2.2.1 In 5.0 liter autoclave charged 2-n-butyl-3-[4-(3-di-n-butylamino-propoxy)benzoyl]-5-nitrobenzofuran (100.0 g) (196.85 mmols), ethanol (1000.0 ml) and 5% Pd/C (10.0 g) (50 % moisture). Hydrogen pressure was applied up to 5.0 Kg/cm2 at 30.0°C and stirred the reaction mass for 6 hours. At the end of this time the reaction mass was filtered through hyflo bed. Filtrate was concentrated to give reddish yellow oil (91.0 g). Molar yield: 96.80% HPLC purity: 95.08%
91% With ammonium chloride; zinc In methanol at 20℃; for 0.5h;
74.2% With iron; ammonium chloride In ethanol; water at 65℃; for 1h; Inert atmosphere; (5-amino-2-butylbenzofuran-3-yl)(4-(3-(dibutylamino)propoxy)phenyl)methanone(6) To a solution of compound 5 (2.17 g,4.27 mmol) in EtOH (21 mL) was added Fe (953 mg, 17.07 mmol), ammonium chlorideaqueous solution (320 mg, 0.59 mmol NH4Cl in 1.5 mL H2O).The mixture was stirred at 65°C for 1 hours. Thereaction mixture was added into water (30 mL) and then extracted with EA (330 mL). The organic phase was dried over Na2SO4,filtered and concentrated to give the crude product, which was purified byflash chromatography [PE/EA=1:1] to give 6 (1.51 g, 74.2%)as a yellow oil. 1H NMR(400 MHz, CDCl3) δ 7.77 (d, J = 8.6 Hz, 2H), 7.19 (d, J = 8.5 Hz,1H), 6.89 (d, J = 8.6 Hz, 2H), 6.62 - 6.56 (m, 2H), 4.05 (t, J = 6.1 Hz, 2H),2.79 (t, J = 7.6 Hz, 2H), 2.65 (t, J = 7.2 Hz, 2H), 2.50 - 2.42 (m, 4H), 1.98 - 1.91 (m, 2H), 1.70 - 1.62 (m, 2H), 1.40 - 1.37 (m, 4H), 1.30- 1.21 (m, 6H), 0.84 (dt, J = 11.6, 7.3 Hz, 9H).
74.2% With iron; ammonium chloride In ethanol; water at 65℃; for 1h; 1 Synthesis of compound 6: Iron (953 mg, 17.07 mmol) and aqueous ammonium chloride solution (320 mg, 0.59 mmol NH4Cl) were added to a solution of compound 5 (2.17 g, 4.27 mmol) in ethanol (21 mL). The mixture was stirred at 65°C for 1 hour. The reaction solution was filtered, and the filtrate was extracted with dichloromethane. The organic phase was dried over anhydrous Na2SO4, filtered, and concentrated to obtain a crude product, which was purified by silica gel column chromatography [petroleum ether/ethyl acetate=1:1] to obtain compound 6 (1.5 g, 74.2%) as a yellow oil.
With hydrogen In ethyl acetate at 25 - 35℃; 2 EXAMPLE 2[0100] Preparation of 5-amino-2-n-butyl-3-[4-(3-di-n- butylaminopropoxy)benzoyl]benzofuran, compound of formula IVa) To a solution of 145g of 2-n-butyl-3-[4-(3-di-n-butylaminopropoxy)benzoyl]-5- nitrobenzofuran, compound of formula III (prepared as in Example 1) in 1450mL of ethyl acetate, flushed twice with nitrogen, was added 7.25g of 10% palladium on carbon (50% wet) at about 25°C to about 30°C. The reaction mass was stirred under hydrogen pressure of about 3kg to about 5kg at about 25°C to about 35°C, till no pressure drop was observed. After completion of reaction, as monitored by high performance liquid chromatography (HPLC), the catalyst was filtered off carefully on a hyflo bed and the hyflo bed was washed with 290mL of ethyl acetate under nitrogen atmosphere. The filtrate and the washings were collected together and concentrated under vacuum to give 130g of pale brown thick oil.Purity (HPLC): 96.76%b) 75.5g of oxalic acid was slowly added at about 25°C to about 30°C to a stirred solution of the oil obtained in (a) in 650mL of ethanol. The reaction mass was stirred for about lh and filtered to give pale yellow solid which was washed with 130mL of ethanol.Yield: 170g170g of the above crude oxalate salt in 1785mL of methanol was stirred under reflux (about 60°C to about 65 °C) to get a clear solution. The reaction mass was stirred at reflux temperature for about 15min and then cooled to about 25°C to about 30°C. The solid obtained was filtered and washed with lOOmL of methanol. Yield: 135 gc) To a stirred mixture of 135g of oxalate salt obtained in (b), lOOOmL of water and 400mL of dichloromethane, was added l lOmL of 1 :1 aqueous ammonia solution drop wise at about 25°C to about 30°C to adjust pH between 8 and 9. The reaction mass was stirred at about 25°C to about 30°C for about 30min. The two layers were separated and the aqueous layer was extracted twice with 400mL of dichloromethane. The organic layers were combined, then washed with water and dried over sodium sulphate. The organic layer was further treated with Norit charcoal, stirred for about 30min at about 25°C to about 30°C and filtered over hyflo bed. The hyflo bed was washed with 250mL of dichloromethane. The combined filtrate and washings were collected together and concentrated under vacuum to give 75g of pale brown thick oil.Purity (HPLC): 98.34%
With ammonium formate In methanol 1 Exapmle-1Preparation of. 5-amino-r2-butyl-3-r4-(3- dibutylamino)propoxy1benzoyl1benzofuranTo a mixture of 2-butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5- nitrobenzofuran (lOgm) and Pd on carbon (10%) (lgm) in methanol (80 ml), ammonium formate (6.20gm) was added followed by stirring for few hours. On completion of a reaction catalyst was filtered and methanol was distilled out under vacuum to give oily mass. To this oily mass dichloromethane (50ml) was added followed by washing it with water (50ml). Layers were separated and organic layer was distilled out to give title compound as oily mass (9.0 gm). HPLC Purity >98%.
Multi-step reaction with 2 steps 1.1: hydrogen / Raney Nickel / methanol / 8 h / 55 °C / 3677.86 Torr 1.2: 0.5 h / 25 - 65 °C 2.1: potassium carbonate / toluene; water / 1 h / 35 °C
Multi-step reaction with 2 steps 1.1: hydrogen / 5%-palladium/activated carbon / methanol / 6 h / 30 °C / 3677.86 Torr / Autoclave 1.2: 2 h / 0 °C / Reflux 2.1: sodium hydroxide / toluene; water / 0.5 h / pH 10 - 12
With hydrogen In isopropyl alcohol at 20℃; for 24h; 2 The above residue (example 1) of 2-«-butyl-3-[4-[3-di-n-butylamino)propoxy]- benzoyl]-5-nitrobenzofuran (6) was dissolved in 2-propanol, 1.6 g (10% palladium on carbon, 50% wet) was added and the mixture was hydrogenated for 24 hours at r.t. After completion of reaction the catalyst was filtered and 7.7 g (0.07 mole) oxalic acid dihydrate was added. The resulting suspension was stirred at r.t. for 2 hours, The solid was filtered and dried to afford 15 g 2-rc-butyl-3-[4-[3-(di-«- butylamino)propoxy] -benzoyl] -5 -aminobenzofuran (7) as a dioxalate salt.
Multi-step reaction with 2 steps 1.1: hydrogen; acetic acid / palladium on activated charcoal / ethyl acetate / 15 - 21 °C / pH 4.5 - 4.8 / Inert atmosphere; Autoclave 1.2: 25 - 35 °C 1.3: 45 - 55 °C 2.1: ammonia / ethyl acetate; water / 25 - 35 °C
With palladium on activated charcoal; ammonium formate In water at 40℃; for 17h; Large scale; EXAMPLE EXAMPLE [0041] a) 2-(n-Butyl)-3-(4-{3-[di(n-butyl)amino]propoxy}benzoyl)-5-aminobenzofuran(Compound A or compound of formula I: R1═n-C4H9; R2═3- [di (n-butyl) amino]propoxy) [0042] 3.33 kg of a 30% solution of 2-(n-butyl)-3-(4-{3-[di(n-butyl)amino]propoxy}benzoyl)-5-nitrobenzofuran (compound of formula II) and 0.05 kg of dry palladium-on-charcoal (Pd/C) are charged to a 5 l reactor at ambient temperature. The combined mixture is heated, with stirring, to 40° C. and then a solution of 0.62 kg (5 equivalents) of ammonium formate in 0.62 kg of water is added over approximately 2 h. The temperature of the reaction medium is then maintained at 40° C. (+/-2° C.) for 15 h while monitoring the progress of the reaction by liquid chromatography. As soon as the reduction is complete, the mixture is cooled to 23° C. (+/-2° C.) and then the palladium-on-charcoal is filtered off and then washed with methyl tert-butyl ether and water. Separation by settling is then carried out at ambient temperature and the organic phase is washed with water. These operations of separation by settling and washing are subsequently repeated once. A further separation by settling is carried out and the solution is concentrated at 40° C. under vacuum. The concentrate is subsequently diluted with tetrahydrofuran, which provides 3.47 kg of a solution of the desired compound in a mixture of methyl tert-butyl ether and of tetrahydrofuran. Estimated yield: 99%
With hydrogen In 2-methyltetrahydrofuran at 60 - 65℃; Autoclave; Large scale;
With 5%-palladium/activated carbon; hydrogen In tetrahydrofuran; tert-butyl methyl ether; water at 30℃; for 10h; Large scale; A2 A2) 2-(n-Butyl)-3-(4-{3-[di(n-butyl)amino]propoxy}benzoyl)-5-aminobenzofuran (Compound A or compound of formula I: R1=n-C4H9; R2=3-[di(n-butyl)amino]propoxy) A1) 2-(n-Butyl)-3-(4-{3-[di(n-butyl)amino]propoxy}benzoyl)-5-aminobenzofuran (Compound A or Compound of Formula I: R1=n-C4H9; R2=3-[di(n-butyl)amino]propoxy) 3.14 kg of 2-(n-butyl)-3-(4-{3-[di-(n-butyl)amino]propoxy}benzoyl)-5-nitrobenzofuran (compound of formula II) at 32% in solution in methyl tert-butyl ether as solvent, and 2.5% weight/weight of palladium-on-charcoal (Pd/C) having a Pd content of 5% and a water content of 50%, are charged, at 20° C., to a hydrogenation apparatus. At the same temperature, the reactor is then purged with nitrogen and hydrogen and then, with stirring, hydrogen under a pressure of 1 bar is introduced, thereby causing an exothermic reaction. The temperature of the reaction medium is raised to 40° C. over the course of 1 hour and is maintained at this temperature for 7 to 8 hours. During this period, the progression of the reaction is verified by liquid chromatography until the starting nitro derivative has disappeared. If necessary, the hydrogenation is continued for a further hour at 40° C. As soon as the reaction has ended, the reactor is purged with nitrogen and then the catalyst is filtered off and rinsed a first time with 0.79 kg of methyl tert-butyl ether and a second time with the same amount of methyl tert-butyl ether. The solution obtained (4.09 kg) is then concentrated at 40° C. under a vacuum of 250 mmHg, which gives a residual volume of 1.5 l. The concentrate is then diluted by adding 2.18 kg (2.45 vol) of tetrahydrofuran so as to obtain a solution of the desired compound in a mixture of methyl tert-butyl ether and of tetrahydrofuran. Estimated yield: 99% According to one variant of the method described in example A1) A2) 2-(n-Butyl)-3-(4-{3-[di(n-butyl)amino]propoxy}benzoyl)-5-aminobenzofuran (Compound A or compound of formula I: R1=n-C4H9; R2=3-[di(n-butyl)amino]propoxy) [0038] 3.14 kg of 2-(n-butyl)-3-(4-{3-[di-(n-butyl)amino]propoxy}benzoyl)-5-nitrobenzofuran (compound of formula II) at a concentration of 35% w/w in solution in methyl tert-butyl ether and tetrahydrofuran (1v/2v) as solvent, and 1.44% weight/weight of palladium-on-charcoal (Pd/C) having a Pd content of 5% and a water content of 50%, are charged, at 20° C., to a hydrogenation apparatus. At the same temperature, the reactor is then purged with nitrogen and hydrogen and then, with stirring, hydrogen under a pressure of 0.2 bar relative is introduced, thereby causing an exothermic reaction. The temperature of the reaction medium is raised to 40° C. over the course of 1 hour and is maintained at this temperature for 3 to hours. During this period, the progression of the reaction is verified by liquid chromatography until the starting nitro derivative has disappeared. If necessary, the hydrogenation is continued for a further hour at 40° C. As soon as the reaction has ended, the reactor is cooled to 20° C. and is purged with nitrogen before filtering off the catalyst, which is rinsed with 2.22 kg of tetrahydrofuran. Estimated yield: 99% [0039] Other tests were carried out starting from a solution of 30% to 35% of 2-(n-butyl)-3-(4-{3-[di-(n-butyl)amino]propoxy}benzoyl)-5-nitrobenzofuran using as catalyst Pd/C at 5% having a water content of 64%. [0040] The following results were recorded: above, Compound A was prepared as follows:
0.112 g With palladium 10% on activated carbon; hydrogen In tetrahydrofuran at 20℃; N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)benzofuran-5yl)methanesulfonamide (51): Compound 49 (0.230 mmol, 0.117 g) was dissolved in THF (3 mL). The flask was capped with a rubber septum and Ar atmosphere was established . Then, Pd/C (10%) (0.028 g) was added, theflask was evacuated, refilled with H2 and equipped with H2-filled balloon. The reaction mixture wasstirred overnight at room temperature. After completion of the reaction, the reaction mixture was filtered through a celite pad, and the pad was washed with AcOEt three times. The solvents wereremoved in vacuo to obtain 50 as a yellow oil (0.112 g) which was used in the next step withoutfurther purification.

Reference: [1]Current Patent Assignee: SANOFI - US2004/10032, 2004, A1 Location in patent: Page/Page column 5;6
[2]Current Patent Assignee: U S V LTD. - EP2428511, 2012, A1 Location in patent: Page/Page column 10
[3]Current Patent Assignee: U S V LTD. - US2012/108828, 2012, A1 Location in patent: Page/Page column 7
[4]Current Patent Assignee: PERMIRA HOLDINGS LIMITED - WO2012/52448, 2012, A1 Location in patent: Page/Page column 10-11
[5]Current Patent Assignee: PERMIRA HOLDINGS LIMITED - EP2447256, 2012, A1 Location in patent: Page/Page column 8
[6]Madhasu, Madhu; Doda, Sai Reddy; Begari, Prem Kumar; Dasari, Krishna Rao; Thalari, Gangadhar; Kadari, Sudhakar; Yadav, Jhillu Singh [Journal of Heterocyclic Chemistry, 2021, vol. 58, # 9, p. 1861 - 1866]
[7]Chen, Hao; Chen, Xiuhui; Sun, Ping; Wu, Dan; Yue, Hu; Pan, Jintao; Li, Xinxuan; Zhang, Cheng; Wu, Xinyi; Hua, Lei; Hu, Wenhui; Yang, Zhongjin [Bioorganic and Medicinal Chemistry Letters, 2021, vol. 46]
[8]Current Patent Assignee: GUANGZHOU MEDICAL UNIVERSITY - CN113200947, 2021, A Location in patent: Paragraph 0053-0055; 0068-0069
[9]Current Patent Assignee: GLENMARK PHARMACEUTICALS LTD - WO2012/7959, 2012, A1 Location in patent: Page/Page column 19-20
[10]Current Patent Assignee: FRICHEM PRIVATE - WO2012/4658, 2012, A2 Location in patent: Page/Page column 18
[11]Current Patent Assignee: ZYDUS LIFESCIENCES LTD - WO2012/32545, 2012, A1
[12]Current Patent Assignee: PERMIRA HOLDINGS LIMITED - EP2447256, 2012, A1
[13]Current Patent Assignee: SUN PHARMACEUTICAL INDUSTRIES LIMITED - WO2012/120544, 2012, A2 Location in patent: Page/Page column 18-19
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[15]Current Patent Assignee: SANOFI - US2013/165675, 2013, A1 Location in patent: Paragraph 0041; 0042
[16]Mali, Anil C.; Ippar, Sharad S.; Bodke, Mahendra B.; Patil, Nilesh S.; Mathad, Vijayavitthal T. [Organic Process Research and Development, 2013, vol. 17, # 5, p. 863 - 868]
[17]Current Patent Assignee: SANOFI - US2015/31901, 2015, A1 Location in patent: Paragraph 0036; 0037; 0038; 0039; 0040
[18]Klucznik, Tomasz; Mikulak-Klucznik, Barbara; McCormack, Michael P.; Lima, Heather; Szymkuć, Sara; Bhowmick, Manishabrata; Molga, Karol; Zhou, Yubai; Rickershauser, Lindsey; Gajewska, Ewa P.; Toutchkine, Alexei; Dittwald, Piotr; Startek, Michał P.; Kirkovits, Gregory J.; Roszak, Rafał; Adamski, Ariel; Sieredzińska, Bianka; Mrksich, Milan; Trice, Sarah L.J.; Grzybowski, Bartosz A. [Chem, 2018, vol. 4, # 3, p. 522 - 532]
  • 2
  • 2-(2-hydroxy-5-nitrophenyl)-1-(4-[3-(dibutylamino)-propoxy]-phenyl)-1,3-heptandione [ No CAS ]
  • [ 141645-23-0 ]
YieldReaction ConditionsOperation in experiment
Stage #1: 2-(2-hydroxy-5-nitrophenyl)-1-(4-[3-(dibutylamino)-propoxy]-phenyl)-1,3-heptandione With 2-methoxyacetic acid In dichloromethane at 75 - 85℃; Stage #2: With potassium hydroxide In dichloromethane; water at 70 - 90℃; for 0.166667h; 10.b b) 1.60 g (3.04 mmol) 2-(2-pentanoyloxy-5-nitrophenyl)-1 -(4-[3-(dibutylamino)- propoxy]-phenyl)-ethanone (a compound of the formula VII, R1 = n-butyl; R2 = 3- [dibutylamino]-propoxy] dissolved in 4 ml of dry dichloromethane were treated under cooling at 15-25°C with 0.57 g (3.34 mmol) of 2-tert.-butyl-1 ,1 ,3,3,-tetramethyl- guanidine. After 15 min the deep orange-red oil was quickly transferred into 2.21 g (24.3 mmol) of methoxy-acetic acid under stirring at 75-85°C. The bright yellow solution was stirred at this temperature for further 12 hours until RP-HPLC analysis confirmed the complete consumption of the intermediate 2-(2-hydroxy-5-nitrophenyl)- 1 -(4-[3-(dibutylamino)-propoxy]-phenyl)-1 ,3-heptandione (compound of the formula VIII wherein R1 is n-butyl and R2 is 3-[dibutylamino]-propoxy, LC-MS: MH+ 527). Then a hot solution of 3.12 g (47.3 mmol) of potassium hydroxide (85% KOH) in 20 ml of water was added under stirring at 70-900C and the stirring was continued for 10 minutes at that temperature. After cooling to room temperature the mixture was extracted with dichloromethane. The organic phase was washed with diluted aqueous NaOH, aqueous potassium dihydrogen phosphate buffer and brine, and then evaporated to dryness. The residue was purified by flash chromatography on silica gel by quick filtration with ethyl acetate as eluent to give 0.80 g (52%) of the title compound as a yellow oil.1H NMR (DMSO-d6): 0.82 (3t, 9H, CH3), 1.20-1.40 (m, 10H1 CH2), 1.68 (m, 2H, 2- butylCH2), 1.85 (m, 2H, OCH2CH2CH2N), 2.35 (m, 4H, CH2N), 2.53 (m, 2H, OCH2CH2CH2N), 2.84 (t, 2H, Ar-CH2), 4.13 (t, 2H OCH2), 7.08 and 7.80 (2d, 4H, Ar- H), 7.93 (m, 1 H, Ar-H), 8.25 (m, 2H, Ar-H). LC-MS: MH+ 509
  • 3
  • [ 141645-16-1 ]
  • [ 36421-15-5 ]
  • [ 141645-23-0 ]
YieldReaction ConditionsOperation in experiment
99.5% Stage #1: 2-n-butyl-3-(4-hydroxybenzoyl)-5-nitrobenzofuran With potassium carbonate In toluene at 25 - 110℃; for 0.5h; Large scale; Stage #2: dibutyl-(3-chloro-propyl)-amine In toluene Reflux; Large scale;
91% Stage #1: 2-n-butyl-3-(4-hydroxybenzoyl)-5-nitrobenzofuran With potassium carbonate In acetonitrile for 0.5h; Stage #2: dibutyl-(3-chloro-propyl)-amine In acetonitrile Reflux; 1 Example 1: Preparation of 2-n-butyl-3-[4-(3-di-n-butylamino-propoxy)benzoyl]-5-nitro benzofuran: A mixture of 2-n-butyl-3-(4-hydroxybenzoyl)-5-nitro benzofuran (119 gm, 0.35 mol) and 48 gm of potassium carbonate in 600 ml of acetonitrile was stirred for 30 min and 1-chloro-3-di-n-butylamino propane (72 gm, 0.35 mol) was added to the mixture. The reaction mixture was heated to reflux for 3 to 4 hr. After completion of the reaction, the mixture was cooled to room temperature. The mixture was filtered and the residue was washed with acetonitrile. The collected filtrate was concentrated to obtain an oily mass. The obtained mass was treated with 5% NaOH (2.5 L) for 10 min followed by extraction with methyl tert butyl ether (MTBE) (2.5 L). The organic layer was dried over sodium sulfate and concentrated to get 162 gm of oily product. Yield: 91%.
91% Stage #1: 2-n-butyl-3-(4-hydroxybenzoyl)-5-nitrobenzofuran With potassium carbonate In acetonitrile for 0.5h; Reflux; Stage #2: dibutyl-(3-chloro-propyl)-amine In acetonitrile Reflux; 1 A mixture of 2-n-butyl-3-(4-hydroxybenzoyl)-5-nitro benzofuran (119 gm, 0.35 mol) and 48 gm of potassium carbonate in 600 ml of acetonitrile was stirred for 30 min and 1-chloro-3-di-n-butylamino propane (72 gm, 0.35 mol) was added to the mixture. The reaction mixture was heated to reflux for 3 to 4 hr. After completion of the reaction, the mixture was cooled to room temperature. The mixture was filtered and the residue was washed with acetonitrile. The collected filtrate was concentrated to obtain an oily mass. The obtained mass was treated with 5% NaOH (2.5 L) for 10 min followed by extraction with methyl tert butyl ether (MTBE) (2.5 L). The organic layer was dried over sodium sulfate and concentrated to get 162 gm of oily product.Yield: 91%.
89.45% Stage #1: 2-n-butyl-3-(4-hydroxybenzoyl)-5-nitrobenzofuran With sodium hydroxide In water for 0.25h; Stage #2: dibutyl-(3-chloro-propyl)-amine In water at 80℃; for 5.25h; 1.1 Example 1.1:In a 250 ml round bottom flask was charged 2-n-butyl-3-(4-hydroxybenzoyl)- 5-nitrobenzofuran (10.0 g) (29.46 mmols), water (50.0 ml) and NaOH (1.18 g) (29.50 mmols) and stirred for 15 minutes. Heated the reaction mass to 80.0°C and charged N,N- dibutyl-3-chloro-l-propanamine (9.09 g) (44.40 mmols) dropwise within 15 minutes. Reaction mass was maintained at 80.0°C for 5 hours. At the end of this time the reaction mass was cooled at 30.0°C and extracted in toluene (150.0 ml). The toluene layer was washed with 10.0% NaOH solution (50.0 mlx2) followed by water wash (50.0 mlx2). Finally the toluene layer was dried over sodium sulphate and concentrated to get reddish yellow oil (13.5 g). Molar yield: 89.45%HPLC purity: 93.22%
89.08% Stage #1: 2-n-butyl-3-(4-hydroxybenzoyl)-5-nitrobenzofuran With sodium hydroxide In water for 0.25h; Stage #2: dibutyl-(3-chloro-propyl)-amine In water at 90℃; for 5.25h; 1.1.2 In a 2.0 liter round bottom flask was charged 2-n-butyl 3-(4- hydroxy benzoyl) 5-nitrobenzofuran (200.0 g) (589.00 mmols), water (600.0 ml) and NaOH (35.39 g) (884.75 mmols) and stirred for 15 minutes. Heated the reaction mass to 90.0°C and charged N,N- dibutyl-3-chloro-1-propanamine (120.45 g) (589.00 mmols) dropwise within 15 minutes. Reaction mass was maintained at 90.0°C for 5 hours. At the end of this time the reaction mass was cooled at 30.0°C and extracted in toluene (1500.0 ml). The toluene layer was washed with water (1000.0 mlx2). Finally the toluene layer was dried over sodium sulphate and concentrated to get reddish yellow oil (258.0 g). Molar yield: 86.08% HPLC purity: 97.92%
85% With potassium carbonate In N,N-dimethyl-formamide at 85℃; for 4h; (2-butyl-5-nitrobenzofuran-3-yl)(4-(3-(dibutylamino)propoxy)phenyl)methanone (49): Compounds 47 (0.730 mmol, 0.248 g), 48 (0.803 mmol, 0.165 g) and K2CO3 (0.730 mmol, 0.101 g)were dissolved in DMF (4.5 mL) and the reaction mixture was stirred at 85 C for 4 hrs. Aftercompletion of the reaction, the reaction mixture was diluted with water and DCM. The aqueous layerwas extracted with DCM three times and the combined organic layers were dried over anhydrous MgSO4 and filtered. The solvents were removed in vacuo and the residue was then purified by flash column chromatography (CHCl3:MeOH, 30:1) to yield 49 as a yellow oil (0.316 g, 85%).1H NMR (400 MHz, CDCl3) δ 8.36 (d, 1H), 8.23 (dd, J = 9.0, 2.3 Hz, 1H), 7.83 (d, J = 8.7 Hz, 2H), 7.57(d, J = 9.0 Hz, 1H), 7.00 (d, J = 8.8 Hz, 2H), 4.14 (t, J = 6.3 Hz, 2H), 2.93 (t, J = 7.6 Hz, 2H), 2.64 (t, J= 6.9 Hz, 2H), 2.51 - 2.38 (m, 4H), 2.03 - 1.91 (m, 2H), 1.83 - 1.72 (m, 2H), 1.48 - 1.40 (m, 4H), 1.38- 1.29 (m, 6H), 0.91 (t, 9H).13C NMR (101 MHz, CDCl3) δ 189.02, 167.01, 163.64, 156.30, 144.64, 131.69, 130.75, 127.94,120.16, 117.69, 117.34, 114.48, 111.33, 66.62, 53.95, 50.33, 29.90, 29.47, 29.06, 27.93, 27.00,22.31, 20.68, 14.05, 13.62.HRMS (ESI+): m/z [M+H+] calcd for C30H41N2O5: 509.3015 , found: 509.3008.
72.4% With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 65℃; for 5h; Inert atmosphere; (2-butyl-5-nitrobenzofuran-3-yl)(4-(3-(dibutylamino)propoxy)phenyl)methanone5 To a solution of compound 4 (2.0 g, 5.90 mmol) in DMF (12 mL) was addedN-butyl-N-(3-chloropropyl)butan-1-amine (1.35 mL, 5.90 mmol), potassium iodide(98 mg, 0.59 mmol) and K2CO3 (0.82 g, 5.90 mmol).The mixture was stirred at 65°C for 5 hours. The reaction mixture was added into water (10 mL) and then extracted with EA (320 mL). The organic phase was washed with brine (50 ml), then dried over Na2SO4,filtered and concentrated to give the crude product, which was purified byflash chromatography [PE/EA=1:1] to give 5 (2.17g, 72.4%) as a yellowoil. 1H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 2.2 Hz,1H), 8.21 - 8.18 (m, 1H), 7.83 - 7.78 (m, 2H), 7.54 (d, J = 9.0 Hz, 1H), 6.96(d, J = 8.9 Hz, 2H), 4.11 (t, J = 6.2 Hz, 2H), 2.90 (t, J = 7.6 Hz, 2H), 2.61(t, J = 7.0 Hz, 2H), 2.45 - 2.40 (m, 4H), 1.98 - 1.90 (m, 2H), 1.78 - 1.70 (m,2H), 1.43 - 1.38 (m, 4H), 1.32 - 1.22 (m, 6H), 0.91 - 0.84 (m, 9H).
72% With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 65℃; for 5h; 1 Synthesis of compound 5: In the DMF (12mL) solution of compound 4 (2.0g, 5.90mmol) was added n-butyl-N-(3-chloropropyl)butan-1-amine (1.35mL, 5.90mmol), potassium iodide (98mg, 0.59mmol) ) And K2CO3 (0.82g, 5.90mmol). The mixture was stirred at 65°C for 5 hours. The reaction mixture was extracted with ethyl acetate. The organic phase was washed with water (50ml), dried over anhydrous Na2SO4, filtered and concentrated to obtain a crude product, which was purified by silica gel column chromatography [petroleum ether/ethyl acetate=1:1] to obtain compound 5 (2.17g, 72.0%) , It is a yellow oil.
Stage #1: 2-n-butyl-3-(4-hydroxybenzoyl)-5-nitrobenzofuran With potassium carbonate In butanone at 20℃; for 0.5h; Stage #2: dibutyl-(3-chloro-propyl)-amine In butanone at 78 - 82℃; for 12h; 1 EXAMPLE 1[0099] Preparation of 2-n-butyl-3-[4-(3-di-n-butylaminopropoxy)benzoyl]-5- nitrobenzofuran, compound of formula IIITo a solution of lOOg of 2-n-butyl-3-(4-hydroxybenzoyl)-5-nitrobenzofuran in l OOOmL of methyl ethyl ketone was added 48.8g of potassium carbonate at about room temperature. The reaction mass was stirred for about 30min and 69.7g of l -chloro-3-di-n- butylaminopropane was added to it. The reaction mass was heated to reflux (about 78°C to about 82°C) and stirred at about the same temperature for about 12h. The reaction mass was then cooled to about room temperature and the insoluble solid was filtered and washed with lOOmL of methyl ethyl ketone. The filtrate and washings were collected together and concentrated under vacuum at about temperature below 50°C to obtain pale brown thick oil which was degassed under vacuum at about temperature below 50°C for about 30min. The oil was then dissolved in 700mL of ethyl acetate at about room temperature and 200mL of water was added to it under stirring. The two layers were separated and the organic layer was washed twice, each with 200mL of water. The organic layer was dried over sodium sulphate and concentrated under vacuum at about temperature below 50°C to give pale brown thick oil which was degassed under vacuum at about temperature below 50°C for about 30min. Yield: 160gPurity (HPLC): 98.71%
With sodium hydroxide In dichloromethane; water at 20℃; for 48h; 1 To a suspension of 10 g (0.03 mole) of 2-n-butyl-3-(4-hydroxybenzoyl)-5- nitrobenzofuran in 50 ml dichloromethane was added 60 ml of 15% aqueous sodium hydroxide solution, 7.2 g (0.04 mole) of l-chloro-3-(di-«-butylamino)propane and 0.2 g (2.0% w/w) of Adogen 464. The mixture was stirred at r.t. for 24 hours, an additional 0.1 g (1% w/w) of Adogen 464 was added and the stirring continued for further 24 hours. The mixture was settled and the product enriched organic layer was separated. The aqueous layer was extracted once with methylene chloride, the combined organic layers were washed with DM water and concentrated under vacuum to obtain residue of 2-«-butyl-3-[4-[3-di-«-butylamino)propoxy]benzoyl]-5- nitrobenzofuran (6) as a gummy mass.
With potassium carbonate In butanone at 20 - 81℃; Reflux; 1 Preparation of 2-n-butyl-3-(4-(3-dibutylaminopropoxy) benzoyl)-5- aminobenzofuran dioxalateIn to a 5.0 lit RBF, 2-n-butyl-3-(4-hydroxybenzoyl)-5-nitrobenzofuran (100 g), Methyl ethyl ketone (600 ml), potassium carbonate (44.69 g) & l-Chloro-3-dibutylaminopropane (66.54 g) was charged at R.T. Heat the reaction mixture to 78+/-3°C (Reflux temperature). Stirred the reaction mixture for 8-10 hr at 78+/-3°C. Cool the reaction mixture to 30+/-5°C. Filter it & distilled out organic layer under vacuum completely up to 50°C. Ethyl acetate and water was added to reaction mixture. The organic layer was separated and aqueous layer was discarded. Charge organic layer & add activated charcoal (2.5 g) at 30+/-5°C. Stir the reaction mass for 30-40 min at 30+/-5°C. Distil out ethyl acetate completely u/v up to 45 °C to obtain 2-n-butyl-3-(4-(3-dibutylaminopropoxy)benzoyl)-5- nitrobenzofuran (oil). Charge Ethyl acetate (750 ml), Acetic acid (-90 ml) up to pH 4.5 -4.8 & Pd/C (15 g) into above obtained oil at R.T. Cool the reaction mixture up to 18+/-3°C. Apply pressure (1+/-2 kg) to the autoclave by Nitrogen gas. Stir the reaction mixture for 10 minutes at 18+/-3°C & release nitrogen gas from autoclave. Apply pressure (4+/-1 kg) to the autoclave by Hydrogen gas and stir for 10 minutes at 18+/-3°C. Release Hydrogen gas from autoclave & maintain pressure (4+/-1 kg) to the autoclave for 3-7 hours at 18+/-3°C. After the completion of the reaction, filter the reaction mass through hyflo bed. Wash the bed with ethyl acetate & charge the filtrate. Charge aq. Ammonia solution in to reaction mass (Aq.ammonia (-25%)) in to water. Stir the reaction mass for 20-30 minutes at 30+/-5°C. Settle the reaction mass followed by separating organic layer & discarding aqueous layer. Distil out the ethyl acetate completely under vacuum at 25- 45°C to obtain oil. Charge Methanol & Oxalic acid dehydrate in the obtained oil. Stir the reaction mixture for 1.5- 2.0 hr at 50+/-5°C. Cool the reaction mass up to 30+/-5°C. Stir the reaction mass at 30+/-5°C for 2.0 -2.5 hours & filter the solid. Wash the solid with methanol & dry the solid at 50+/-5°C to obtain the desired product.

Reference: [1]Mali, Anil C.; Ippar, Sharad S.; Bodke, Mahendra B.; Patil, Nilesh S.; Mathad, Vijayavitthal T. [Organic Process Research and Development, 2013, vol. 17, # 5, p. 863 - 868]
[2]Current Patent Assignee: U S V LTD. - EP2428511, 2012, A1 Location in patent: Page/Page column 10
[3]Current Patent Assignee: U S V LTD. - US2012/108828, 2012, A1 Location in patent: Page/Page column 6; 7
[4]Current Patent Assignee: PERMIRA HOLDINGS LIMITED - WO2012/52448, 2012, A1 Location in patent: Page/Page column 9-10
[5]Current Patent Assignee: PERMIRA HOLDINGS LIMITED - EP2447256, 2012, A1 Location in patent: Page/Page column 7-8
[6]Klucznik, Tomasz; Mikulak-Klucznik, Barbara; McCormack, Michael P.; Lima, Heather; Szymkuć, Sara; Bhowmick, Manishabrata; Molga, Karol; Zhou, Yubai; Rickershauser, Lindsey; Gajewska, Ewa P.; Toutchkine, Alexei; Dittwald, Piotr; Startek, Michał P.; Kirkovits, Gregory J.; Roszak, Rafał; Adamski, Ariel; Sieredzińska, Bianka; Mrksich, Milan; Trice, Sarah L.J.; Grzybowski, Bartosz A. [Chem, 2018, vol. 4, # 3, p. 522 - 532]
[7]Chen, Hao; Chen, Xiuhui; Sun, Ping; Wu, Dan; Yue, Hu; Pan, Jintao; Li, Xinxuan; Zhang, Cheng; Wu, Xinyi; Hua, Lei; Hu, Wenhui; Yang, Zhongjin [Bioorganic and Medicinal Chemistry Letters, 2021, vol. 46]
[8]Current Patent Assignee: GUANGZHOU MEDICAL UNIVERSITY - CN113200947, 2021, A Location in patent: Paragraph 0053-0055; 0066-0067
[9]Current Patent Assignee: GLENMARK PHARMACEUTICALS LTD - WO2012/7959, 2012, A1 Location in patent: Page/Page column 19
[10]Current Patent Assignee: SUN PHARMACEUTICAL INDUSTRIES LIMITED - WO2012/120544, 2012, A2 Location in patent: Page/Page column 18
[11]Current Patent Assignee: ALEMBIC PHARMACEUTICALS LIMITED - WO2012/153225, 2012, A1 Location in patent: Page/Page column 2; 12
  • 4
  • [ 141645-23-0 ]
  • [ 141626-36-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: hydrogen / palladium 10% on activated carbon / ethyl acetate / 25 - 35 °C 2.1: triethylamine / dichloromethane / 0.5 h / 20 °C 2.2: 1.5 h / 20 °C
Multi-step reaction with 3 steps 1: hydrogen / Raney nickel / methanol / 45 - 50 °C / 3677.86 Torr 2: tetramethlyammonium chloride / toluene / Reflux 3: sodium hydroxide / 1 h / 0 - 5 °C
Multi-step reaction with 3 steps 1: ammonium formate / palladium 10% on activated carbon / methanol 2: water / 2 h 3: ammonia / dichloromethane
Multi-step reaction with 3 steps 1.1: hydrogen / Raney Nickel / methanol / 8 h / 55 °C / 3677.86 Torr 1.2: 0.5 h / 25 - 65 °C 2.1: potassium carbonate / toluene; water / 1 h / 35 °C 3.1: toluene / 3.5 h / 108 °C 3.2: 0.5 h / 60 °C
Multi-step reaction with 2 steps 1: hydrogen / 5%-palladium/activated carbon / ethanol / 6 h / 30 °C / 3677.86 Torr / Autoclave 2: toluene / 3 h / Reflux
Multi-step reaction with 2 steps 1.1: hydrogen / 5%-palladium/activated carbon / ethanol / 6 h / 30 °C / 3677.86 Torr / Autoclave 2.1: toluene / 3 h / Reflux 2.2: 0.17 h / 30 °C
Multi-step reaction with 3 steps 1.1: hydrogen / 5%-palladium/activated carbon / methanol / 6 h / 30 °C / 3677.86 Torr / Autoclave 1.2: 2 h / 0 °C / Reflux 2.1: sodium hydroxide / toluene; water / 0.5 h / pH 10 - 12 3.1: toluene / 3 h / Reflux 3.2: 0.17 h / 30 °C
Multi-step reaction with 3 steps 1: hydrogen / Raney nickel / methanol / 20 °C / 3677.86 Torr 2: tetramethlyammonium chloride / toluene / Reflux 3: sodium hydroxide / 1 h / 0 - 5 °C
Multi-step reaction with 3 steps 1.1: hydrogen; acetic acid / palladium on activated charcoal / ethyl acetate / 15 - 21 °C / pH 4.5 - 4.8 / Inert atmosphere; Autoclave 1.2: 25 - 35 °C 1.3: 45 - 55 °C 2.1: ammonia / ethyl acetate; water / 25 - 35 °C 3.1: pyridine / dichloromethane / -5 - 5 °C
Multi-step reaction with 2 steps 1: hydrogen; palladium 10% on activated carbon / tetrahydrofuran / 20 °C 2: pyridine / dichloromethane / 1.5 h / 20 °C
Multi-step reaction with 2 steps 1: ammonium chloride; zinc / methanol / 0.5 h / 20 °C 2: sodium hydrogencarbonate / dichloromethane / 6 h / 35 °C / Reflux

  • 5
  • [ 141645-23-0 ]
  • [ 141626-57-5 ]
  • [ 141626-36-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: hydrogen / palladium 10% on activated carbon / ethyl acetate / 25 - 35 °C 2: triethylamine / dichloromethane / 0.5 h / 20 °C
Multi-step reaction with 2 steps 1: palladium on activated charcoal; ammonium formate / 55 °C 2: organic base / dichloromethane
  • 6
  • [ 141645-23-0 ]
  • dronedarone hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: hydrogen / palladium 10% on activated carbon / ethyl acetate / 25 - 35 °C 2.1: triethylamine / dichloromethane / 0.5 h / 20 °C 2.2: 1.5 h / 20 °C 3.1: hydrogenchloride / water; acetone / 3.5 h / 5 - 10 °C / pH 2.5 - 3
Multi-step reaction with 3 steps 1: hydrogen / palladium 10% on activated carbon / ethyl acetate / 25 - 35 °C 2: triethylamine / dichloromethane / 0.5 h / 20 °C 3: hydrogenchloride / water; acetone / 3.5 h / 5 - 10 °C / pH 2.5 - 3
Multi-step reaction with 2 steps 1: hydrogen / Raney nickel / methanol / 45 - 50 °C / 3677.86 Torr 2: tetramethlyammonium chloride / toluene / Reflux
Multi-step reaction with 2 steps 1: ammonium formate / palladium 10% on activated carbon / methanol 2: water / 2 h
Multi-step reaction with 3 steps 1.1: hydrogen / 5%-palladium/activated carbon / ethanol / 6 h / 30 °C / 3677.86 Torr / Autoclave 2.1: toluene / 3 h / Reflux 3.1: chloro-trimethyl-silane / ethyl acetate / 0.17 h / 30 °C 3.2: pH 2 - 3
Multi-step reaction with 3 steps 1.1: hydrogen / 5%-palladium/activated carbon / ethanol / 6 h / 30 °C / 3677.86 Torr / Autoclave 2.1: toluene / 3 h / Reflux 2.2: 0.17 h / 30 °C 3.1: chloro-trimethyl-silane / ethyl acetate; water / 3.17 h / 30 °C / pH 2 - 3
Multi-step reaction with 4 steps 1.1: hydrogen / 5%-palladium/activated carbon / methanol / 6 h / 30 °C / 3677.86 Torr / Autoclave 1.2: 2 h / 0 °C / Reflux 2.1: sodium hydroxide / toluene; water / 0.5 h / pH 10 - 12 3.1: toluene / 3 h / Reflux 3.2: 0.17 h / 30 °C 4.1: chloro-trimethyl-silane / ethyl acetate; water / 3.17 h / 30 °C / pH 2 - 3
Multi-step reaction with 2 steps 1: hydrogen / Raney nickel / methanol / 20 °C / 3677.86 Torr 2: tetramethlyammonium chloride / toluene / Reflux
Multi-step reaction with 2 steps 1: hydrogen / palladium 10% on activated carbon / isopropyl alcohol / 24 h / 20 °C 2: toluene / 2 h / 80 - 85 °C
Multi-step reaction with 4 steps 1.1: hydrogen; acetic acid / palladium on activated charcoal / ethyl acetate / 15 - 21 °C / pH 4.5 - 4.8 / Inert atmosphere; Autoclave 1.2: 25 - 35 °C 1.3: 45 - 55 °C 2.1: ammonia / ethyl acetate; water / 25 - 35 °C 3.1: pyridine / dichloromethane / -5 - 5 °C 4.1: hydrogenchloride / ethyl acetate; water / 20 - 30 °C / pH 2 - 3
Multi-step reaction with 2 steps 1: palladium on activated charcoal; ammonium formate / 55 °C 2: sodium hydrogencarbonate / dichloromethane; hexane

  • 7
  • [ 141645-23-0 ]
  • [ 1354567-97-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: ammonium formate / palladium 10% on activated carbon / methanol 2: water / 2 h 3: ammonia / dichloromethane 4: hydrogen bromide / ethyl acetate
Multi-step reaction with 4 steps 1.1: hydrogen / Raney Nickel / methanol / 8 h / 55 °C / 3677.86 Torr 1.2: 0.5 h / 25 - 65 °C 2.1: potassium carbonate / toluene; water / 1 h / 35 °C 3.1: toluene / 3.5 h / 108 °C 3.2: 0.5 h / 60 °C 4.1: hydrogen bromide / ethyl acetate; hexane / 1 h / 25 - 65 °C
  • 8
  • [ 141645-23-0 ]
  • [ 1354567-98-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: ammonium formate / palladium 10% on activated carbon / methanol 2: hydrogenchloride / dichloromethane / pH 0.5 - 1.5
  • 9
  • [ 100-07-2 ]
  • [ 141645-23-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: aluminum (III) chloride / chlorobenzene / 2 h / 25 °C / Reflux 2.1: aluminum (III) chloride / chlorobenzene / 2 h / 75 °C 2.2: 0.5 h / 5 - 65 °C 3.1: potassium carbonate / butanone / 20 h / 85 °C 3.3: 0.5 h / 25 - 65 °C 4.1: potassium carbonate / toluene; water
Multi-step reaction with 3 steps 1: aluminum (III) chloride / dichloromethane 2: aluminum (III) chloride / chlorobenzene 3: sodium carbonate / toluene; isopropyl alcohol
Multi-step reaction with 3 steps 1.1: aluminum (III) chloride / dichloromethane / 22 h / 25 - 30 °C / Large scale 2.1: aluminum (III) chloride / 40 h / Reflux; Large scale 2.2: 15 °C / Large scale 3.1: potassium carbonate / toluene / 0.5 h / 25 - 110 °C / Large scale 3.2: Reflux; Large scale
  • 10
  • [ 141645-23-0 ]
  • [ 144-62-7 ]
  • 5-amino-2-n-butyl-3-[4-(3-di-n-butylamino propoxy)benzoyl]benzofuran bisoxalate [ No CAS ]
YieldReaction ConditionsOperation in experiment
69.49% Stage #1: (2-butyl-5-nitrobenzofuran-3-yl)(4-(3-(dibutylamino)propoxy)phenyl)methanone With hydrogen In methanol at 30℃; for 6h; Autoclave; Stage #2: oxalic acid In methanol at 0℃; for 2h; Reflux; 3 In 1.0 L autoclave charged 2-n-butyl 3-[4 (3-di-n-butylamino-propoxy) benzoyl] 5- nitrobenzofuran (20.0 g) (39.37 mmols), methanol (140.0 ml) and 5% Pd/C (2.0g) (50 % moisture). Hydrogen pressure was applied up to 5.0 Kg/cm2 at 30.0°C and stirred the reaction mass for 6 hours. At the end of this time the reaction mass was filtered through hyflo bed. Filtrate was collected and transferred in 250.0 ml round bottom flask (Small sample was isolated and analyzed HPLC purity 92.36%). To this solution of 5-amino-3-[4-(3-di-n-butylamino-propoxy)benzoyl]-2-n-butylbenzofuran in methanol was added oxalic acid (7.78 g) (86.44 mmols) in one lot and heated the reaction mass to reflux for 1 hour. The reaction mass was cooled to 0°C and stirred for 1 hour. The precipitated solid was filtered and dried at 50.0°C under vacuum for 2 hours. (Dry weight: 18.0 g) Molar yield: 69.49% HPLC purity: 98.64%
Stage #1: (2-butyl-5-nitrobenzofuran-3-yl)(4-(3-(dibutylamino)propoxy)phenyl)methanone With hydrogen In methanol at 55℃; for 8h; Stage #2: oxalic acid In methanol at 25 - 65℃; for 0.5h; 4.1.A Example-4: -Preparation of 5-amino 3-f4-(3-di-n-butylamino-propoxy)benzoyll-2-n-butyl benzofuranMethod-l:(A) 5-amino 3-f4-(3-di-n-butylamino-propoxy)benzoyll-2-n-butyl benzofuran dioxalate salt100 g 2-n-butyl-3-[4-(3-di-n-butylamino-propoxy)benzoyl]-5-nitro benzofuran, 700 mL methanol and 15 g of Raney Nickel were taken under nitrogen atmosphere at 25°C in 2.0 L autoclave. Hydrogen pressure of 0.5-1.0 Kg was flushed two times and released at 25°C. The hydrogen pressure upto 3.0 Kg/cm2 was applied and the reaction mixture was heated to 55°C. Further the pressure was increased to 5.0 Kg/cm2 and maintained for 8 hours at 55°C. After the completion of the reaction as monitored by TLC, the reaction mixture was cooled to 25°C. The reaction mixture was flushed with nitrogen pressure two times and filtered under nitrogen atmosphere at 25°C followed by washing with 50 mL methanol. The filtrate was distilled under vacuum at 65°C to obtain residue. The residue was dissolved in methanol at 25°C and 52.20 g oxalic acid solution in methanol was added. The reaction mixture was heated to 65°C and stirred for 30 min at 50°C followed by cooling to 25°C. The product was filtered and washed with methanol and dried to obtain 5-amino 3-[4-(3-di-n-butylamino-propoxy)benzoyl]- 2-n-butyl benzofuran dioxalate salt. Purity > 98% (HPLC)The dioxalate salt is characterized by XRD substantially as depicted in FIG.17 and DSC substantially as depicted in FIG.18
Stage #1: (2-butyl-5-nitrobenzofuran-3-yl)(4-(3-(dibutylamino)propoxy)phenyl)methanone With hydrogen; acetic acid In ethyl acetate at 15 - 21℃; Inert atmosphere; Autoclave; Stage #2: With ammonia In water; ethyl acetate at 25 - 35℃; Stage #3: oxalic acid In methanol at 45 - 55℃; 1 Preparation of 2-n-butyl-3-(4-(3-dibutylaminopropoxy) benzoyl)-5- aminobenzofuran dioxalateIn to a 5.0 lit RBF, 2-n-butyl-3-(4-hydroxybenzoyl)-5-nitrobenzofuran (100 g), Methyl ethyl ketone (600 ml), potassium carbonate (44.69 g) & l-Chloro-3-dibutylaminopropane (66.54 g) was charged at R.T. Heat the reaction mixture to 78+/-3°C (Reflux temperature). Stirred the reaction mixture for 8-10 hr at 78+/-3°C. Cool the reaction mixture to 30+/-5°C. Filter it & distilled out organic layer under vacuum completely up to 50°C. Ethyl acetate and water was added to reaction mixture. The organic layer was separated and aqueous layer was discarded. Charge organic layer & add activated charcoal (2.5 g) at 30+/-5°C. Stir the reaction mass for 30-40 min at 30+/-5°C. Distil out ethyl acetate completely u/v up to 45 °C to obtain 2-n-butyl-3-(4-(3-dibutylaminopropoxy)benzoyl)-5- nitrobenzofuran (oil). Charge Ethyl acetate (750 ml), Acetic acid (-90 ml) up to pH 4.5 -4.8 & Pd/C (15 g) into above obtained oil at R.T. Cool the reaction mixture up to 18+/-3°C. Apply pressure (1+/-2 kg) to the autoclave by Nitrogen gas. Stir the reaction mixture for 10 minutes at 18+/-3°C & release nitrogen gas from autoclave. Apply pressure (4+/-1 kg) to the autoclave by Hydrogen gas and stir for 10 minutes at 18+/-3°C. Release Hydrogen gas from autoclave & maintain pressure (4+/-1 kg) to the autoclave for 3-7 hours at 18+/-3°C. After the completion of the reaction, filter the reaction mass through hyflo bed. Wash the bed with ethyl acetate & charge the filtrate. Charge aq. Ammonia solution in to reaction mass (Aq.ammonia (-25%)) in to water. Stir the reaction mass for 20-30 minutes at 30+/-5°C. Settle the reaction mass followed by separating organic layer & discarding aqueous layer. Distil out the ethyl acetate completely under vacuum at 25- 45°C to obtain oil. Charge Methanol & Oxalic acid dehydrate in the obtained oil. Stir the reaction mixture for 1.5- 2.0 hr at 50+/-5°C. Cool the reaction mass up to 30+/-5°C. Stir the reaction mass at 30+/-5°C for 2.0 -2.5 hours & filter the solid. Wash the solid with methanol & dry the solid at 50+/-5°C to obtain the desired product.
With palladium on activated charcoal; ammonium formate at 55℃;

  • 11
  • [ 133238-87-6 ]
  • [ 141645-23-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: aluminum (III) chloride / chlorobenzene / 2 h / 25 °C / Reflux 2.1: aluminum (III) chloride / chlorobenzene / 2 h / 75 °C 2.2: 0.5 h / 5 - 65 °C 3.1: potassium carbonate / butanone / 20 h / 85 °C 3.3: 0.5 h / 25 - 65 °C 4.1: potassium carbonate / toluene; water
Multi-step reaction with 3 steps 1: aluminum (III) chloride / dichloromethane 2: aluminum (III) chloride / chlorobenzene 3: sodium carbonate / toluene; isopropyl alcohol
Multi-step reaction with 3 steps 1.1: aluminum (III) chloride / dichloromethane / 22 h / 25 - 30 °C / Large scale 2.1: aluminum (III) chloride / 40 h / Reflux; Large scale 2.2: 15 °C / Large scale 3.1: potassium carbonate / toluene / 0.5 h / 25 - 110 °C / Large scale 3.2: Reflux; Large scale
Multi-step reaction with 3 steps 1: aluminum (III) chloride / dichloromethane / 24 h / 20 °C / Inert atmosphere 2: aluminum (III) chloride / chlorobenzene / 2 h / 80 °C / Inert atmosphere 3: potassium iodide; potassium carbonate / N,N-dimethyl-formamide / 5 h / 65 °C / Inert atmosphere
Multi-step reaction with 3 steps 1: aluminum (III) chloride / dichloromethane / 24 h / 20 °C 2: aluminum (III) chloride / chlorobenzene / 2 h / 80 °C 3: potassium carbonate; potassium iodide / N,N-dimethyl-formamide / 5 h / 65 °C

  • 12
  • [ 141645-16-1 ]
  • [ 141645-23-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: potassium carbonate / butanone / 20 h / 85 °C 1.3: 0.5 h / 25 - 65 °C 2.1: potassium carbonate / toluene; water
  • 13
  • [ 141645-23-0 ]
  • 2-butyl-3-(4-[3-(dibutylamino)propoxy]benzoyl)-5-methansulfonylamino-benzofuran sulfate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: hydrogen / Raney Nickel / methanol / 8 h / 55 °C / 3677.86 Torr 1.2: 0.5 h / 25 - 65 °C 2.1: potassium carbonate / toluene; water / 1 h / 35 °C 3.1: toluene / 3.5 h / 108 °C 3.2: 0.5 h / 60 °C 4.1: sulfuric acid / ethyl acetate / 1 h / 25 - 70 °C
  • 15
  • 2-n-butyl-3-[4-(3-di-n-butylaminopropoxy)benzoyl]-5-nitrobenzofuran oxalate salt [ No CAS ]
  • [ 141645-23-0 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate In water; toluene 3.B (B) 2-n-butyl 3-f4-f3-di-n-butvIamino-propoxy)benzoyIl-5-nitro benzofuranThe oxalate salt obtained in step (A) was converted to 2-n-butyl-3-[4-(3-di-n- butylamino-propoxy)benzoyl]-5-nitro benzofuran free base by treatment with potassium carbonate in biphasic solvent system toluene and water. The residue was isolated by removal of solvent by distillation under vacuum. Purity > 99.5% (HPLC).
  • 16
  • [ 141645-23-0 ]
  • (5-amino-2-butyl-1-benzofuran-3-yl)[4-[3-(di-n-butylamino)propoxy]phenyl]-methanone dihydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
99% With hydrogenchloride; hydrogen In ethanol; water at 50℃; for 4h; 7 5.08 g of (2-n-butyl-5-nitro-l-benzofuran-3-yl)[4-(di-n-butylamino)propoxy]- phenyl] methanone (III) is dissolved in 50 ml of ethanol and 0.3 g of Pd/C (10 %) is added. Under stirring 1.8 ml of hydrochlorid acid ( 37%) is added to the mixture and heated to 50 °C and is set under H2 pressure of 10 bar. After 4 hours reaction time the mixture is cooled down to room temperature, the catalyst is filtered and the solvent is evaporated under reduced pressure.Yield: 5.5 g (99 %). Purity of product (HPLC): 97.6 %.The product is identical with compound prepared in Example 6
  • 17
  • [ 99-93-4 ]
  • [ 141645-23-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: potassium carbonate / butanone / Reflux 2: sodium methylate / 1-methyl-pyrrolidin-2-one / 5 - 20 °C 3: acetic acid / 12 h / 20 °C 4: acetic acid / 6 h / 117 °C
  • 18
  • [ 36421-15-5 ]
  • [ 141645-23-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: potassium carbonate / butanone / Reflux 2: sodium methylate / 1-methyl-pyrrolidin-2-one / 5 - 20 °C 3: acetic acid / 12 h / 20 °C 4: acetic acid / 6 h / 117 °C
Multi-step reaction with 5 steps 1.1: potassium carbonate / acetone / 4 h / 20 °C / Reflux 2.1: n-butyllithium / tetrahydrofuran / 1.33 h / -78 - 20 °C 2.2: 1.5 h / -78 - 20 °C 3.1: manganese(IV) oxide / dichloromethane / 2 h / 20 °C 4.1: potassium phosphate tribasic / acetonitrile / 75 °C 5.1: triphenylphosphine; palladium diacetate; silver carbonate / acetonitrile / 15 h / 115 °C / Inert atmosphere
  • 19
  • [ 1257220-36-2 ]
  • [ 141645-23-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium methylate / 1-methyl-pyrrolidin-2-one / 5 - 20 °C 2: acetic acid / 12 h / 20 °C 3: acetic acid / 6 h / 117 °C
  • 20
  • [ 1333493-60-9 ]
  • [ 141645-23-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium hydrogencarbonate / water 2: acetic acid / 12 h / 20 °C 3: acetic acid / 6 h / 117 °C
  • 21
  • 1-chloro-3-(di-n-butylamino)-propane hydrochloride [ No CAS ]
  • [ 141645-23-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: ammonium hydroxide / water / 0.25 h / 20 - 25 °C 2: potassium carbonate / butanone / Reflux 3: sodium methylate / 1-methyl-pyrrolidin-2-one / 5 - 20 °C 4: acetic acid / 12 h / 20 °C 5: acetic acid / 6 h / 117 °C
  • 22
  • [ 1356411-44-3 ]
  • [ 141645-23-0 ]
YieldReaction ConditionsOperation in experiment
Stage #1: C30H43N3O5 In acetic acid at 117℃; for 6h; Stage #2: With sodium carbonate In ethyl acetate 1 EXAMPLE 1 2-n-Butyl-3-{4-[3-(di-n-butylamino)propoxy]benzoyl}-5-nitrobenzofuran (Compound I: R1=n-C4H9; R2=3-(di-n-butylamino)propoxy) 7.11 g of 1-{4-[3-(di-n-butylamino)propoxy]phenyl}-1,3-heptanedione (compound XII or III) (optical purity: 95%; 17 mmol), 2.81 g of O-(4-nitrophenyl)hydroxylamine (compound II) (18 mmol) and 34 ml of acetic acid are placed in a 100 ml Keller flask. The mixture is stirred at room temperature for 12 hours (formation of the oxime of formula IV: R1=n-C4H9; R2=3-(di-n-butylamino)propoxy) and is then refluxed (117° C.) for 6 hours. The reaction medium is evaporated to dryness on a rotary evaporator and the crude reaction product is diluted with 60 ml of ethyl acetate. The resulting solution is then hydrolyzed by addition of 100 ml of basic sodium carbonate solution (20 w/w %), the phases are separated by settling and the organic phase is washed with three times 100 ml of water to neutral pH. The organic phase is dried over sodium sulfate, the suspension is filtered and the solvent is evaporated off to dryness using a rotary evaporator. Mass obtained: 9.01 g Appearance: colored oil Titer of the crude product by TLC: 67% Chemical yield: 69%
  • 23
  • [ 504421-91-4 ]
  • [ 141645-23-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine / tetrahydrofuran / 5.5 h / 20 °C / Inert atmosphere 2: tetrakis(triphenylphosphine) palladium(0); potassium carbonate / 24 h / 55 °C / Sealed tube 3: potassium carbonate / N,N-dimethyl-formamide / 4 h / 85 °C
  • 24
  • [ 1636167-45-7 ]
  • [ 141645-23-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: tetrakis(triphenylphosphine) palladium(0); potassium carbonate / 24 h / 55 °C / Sealed tube 2: potassium carbonate / N,N-dimethyl-formamide / 4 h / 85 °C
  • 25
  • [ 33527-94-5 ]
  • [ 141645-23-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: tetrakis(triphenylphosphine) palladium(0); potassium carbonate / 24 h / 55 °C / Sealed tube 2: potassium carbonate / N,N-dimethyl-formamide / 4 h / 85 °C
  • 27
  • [ 89487-91-2 ]
  • [ 141645-23-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: triethylamine / tetrahydrofuran; dichloromethane / 4 h / 0 - 20 °C 2: copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine / tetrahydrofuran / 5.5 h / 20 °C / Inert atmosphere 3: tetrakis(triphenylphosphine) palladium(0); potassium carbonate / 24 h / 55 °C / Sealed tube 4: potassium carbonate / N,N-dimethyl-formamide / 4 h / 85 °C
  • 28
  • [ 540-38-5 ]
  • [ 141645-23-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: dmap; triethylamine / dichloromethane / 1.5 h / 20 °C 2: tetrakis(triphenylphosphine) palladium(0); potassium carbonate / 24 h / 55 °C / Sealed tube 3: potassium carbonate / N,N-dimethyl-formamide / 4 h / 85 °C
  • 29
  • [ 111-92-2 ]
  • [ 141645-23-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: methanol / 8 h / 20 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 8 h / 20 °C 3: thionyl chloride / chloroform / 7 h / Reflux 4: potassium carbonate / N,N-dimethyl-formamide / 4 h / 85 °C
  • 30
  • [ 20120-23-4 ]
  • [ 141645-23-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: lithium aluminium tetrahydride / tetrahydrofuran / 8 h / 20 °C 2: thionyl chloride / chloroform / 7 h / Reflux 3: potassium carbonate / N,N-dimethyl-formamide / 4 h / 85 °C
  • 31
  • [ 772-33-8 ]
  • [ 141645-23-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: triphenylphosphine / dichloromethane / 1 h / 40 °C / Inert atmosphere 1.2: 3 h / 110 °C / Inert atmosphere 2.1: aluminum (III) chloride / dichloromethane / 24 h / 20 °C / Inert atmosphere 3.1: aluminum (III) chloride / chlorobenzene / 2 h / 80 °C / Inert atmosphere 4.1: potassium iodide; potassium carbonate / N,N-dimethyl-formamide / 5 h / 65 °C / Inert atmosphere
Multi-step reaction with 4 steps 1.1: triphenylphosphine / dichloromethane / 1 h / 40 °C 1.2: 3 h / 110 °C 2.1: aluminum (III) chloride / dichloromethane / 24 h / 20 °C 3.1: aluminum (III) chloride / chlorobenzene / 2 h / 80 °C 4.1: potassium carbonate; potassium iodide / N,N-dimethyl-formamide / 5 h / 65 °C
  • 32
  • [ 638-29-9 ]
  • [ 141645-23-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: triphenylphosphine / dichloromethane / 1 h / 40 °C / Inert atmosphere 1.2: 3 h / 110 °C / Inert atmosphere 2.1: aluminum (III) chloride / dichloromethane / 24 h / 20 °C / Inert atmosphere 3.1: aluminum (III) chloride / chlorobenzene / 2 h / 80 °C / Inert atmosphere 4.1: potassium iodide; potassium carbonate / N,N-dimethyl-formamide / 5 h / 65 °C / Inert atmosphere
Multi-step reaction with 4 steps 1.1: triphenylphosphine / dichloromethane / 1 h / 40 °C 1.2: 3 h / 110 °C 2.1: aluminum (III) chloride / dichloromethane / 24 h / 20 °C 3.1: aluminum (III) chloride / chlorobenzene / 2 h / 80 °C 4.1: potassium carbonate; potassium iodide / N,N-dimethyl-formamide / 5 h / 65 °C
  • 33
  • [ 141645-23-0 ]
  • N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)benzofuran-5-yl)cyclohexanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: iron; ammonium chloride / ethanol; water / 1 h / 65 °C / Inert atmosphere 2: triethylamine / 5,5-dimethyl-1,3-cyclohexadiene / 2 h / 60 °C / Inert atmosphere
  • 34
  • [ 141645-23-0 ]
  • N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)benzofuran-5-yl)benzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: iron; ammonium chloride / ethanol; water / 1 h / 65 °C / Inert atmosphere 2: triethylamine / 5,5-dimethyl-1,3-cyclohexadiene / 2 h / 60 °C / Inert atmosphere
  • 35
  • [ 141645-23-0 ]
  • N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)benzofuran-5-yl)pyridine-3-sulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: iron; ammonium chloride / ethanol; water / 1 h / 65 °C / Inert atmosphere 2: triethylamine / 5,5-dimethyl-1,3-cyclohexadiene / 2 h / 60 °C / Inert atmosphere
  • 36
  • [ 141645-23-0 ]
  • N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)benzofuran-5-yl)-4-methylbenzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: iron; ammonium chloride / ethanol; water / 1 h / 65 °C / Inert atmosphere 2: triethylamine / 5,5-dimethyl-1,3-cyclohexadiene / 2 h / 60 °C / Inert atmosphere
  • 37
  • [ 141645-23-0 ]
  • N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)benzofuran-5-yl)-4-fluorobenzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: iron; ammonium chloride / ethanol; water / 1 h / 65 °C / Inert atmosphere 2: triethylamine / 5,5-dimethyl-1,3-cyclohexadiene / 2 h / 60 °C / Inert atmosphere
  • 38
  • [ 141645-23-0 ]
  • N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)benzofuran-5-yl)-4-(trifluoromethyl)benzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: iron; ammonium chloride / ethanol; water / 1 h / 65 °C / Inert atmosphere 2: triethylamine / 5,5-dimethyl-1,3-cyclohexadiene / 2 h / 60 °C / Inert atmosphere
  • 39
  • [ 141645-23-0 ]
  • N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)benzofuran-5-yl)-4-methoxybenzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: iron; ammonium chloride / ethanol; water / 1 h / 65 °C / Inert atmosphere 2: triethylamine / 5,5-dimethyl-1,3-cyclohexadiene / 2 h / 60 °C / Inert atmosphere
  • 40
  • [ 141645-23-0 ]
  • [ 1278585-69-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: iron; ammonium chloride / ethanol; water / 1 h / 65 °C / Inert atmosphere 2: triethylamine / 5 h / 20 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: ammonium chloride; iron / water; ethanol / 1 h / 65 °C 2: triethylamine / 5,5-dimethyl-1,3-cyclohexadiene / 5 h / 20 °C
  • 41
  • [ 141645-23-0 ]
  • N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)benzofuran-5-yl)acrylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: iron; ammonium chloride / ethanol; water / 1 h / 65 °C / Inert atmosphere 2: triethylamine / 5 h / 20 °C / Inert atmosphere
  • 42
  • [ 141645-23-0 ]
  • N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)benzofuran-5-yl)isobutyramide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: iron; ammonium chloride / ethanol; water / 1 h / 65 °C / Inert atmosphere 2: triethylamine / 5 h / 20 °C / Inert atmosphere
  • 43
  • [ 141645-23-0 ]
  • N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)benzofuran-5-yl)pentanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: iron; ammonium chloride / ethanol; water / 1 h / 65 °C / Inert atmosphere 2: triethylamine / 5 h / 20 °C / Inert atmosphere
  • 44
  • [ 141645-23-0 ]
  • N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)benzofuran-5-yl)pivalamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: iron; ammonium chloride / ethanol; water / 1 h / 65 °C / Inert atmosphere 2: triethylamine / 5 h / 20 °C / Inert atmosphere
  • 45
  • [ 141645-23-0 ]
  • N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)benzofuran-5-yl)benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: iron; ammonium chloride / ethanol; water / 1 h / 65 °C / Inert atmosphere 2: triethylamine / 5 h / 20 °C / Inert atmosphere
  • 46
  • [ 141645-23-0 ]
  • N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)benzofuran-5-yl)-4-methoxybenzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: iron; ammonium chloride / ethanol; water / 1 h / 65 °C / Inert atmosphere 2: triethylamine / 5 h / 20 °C / Inert atmosphere
  • 47
  • [ 141645-23-0 ]
  • 1-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)benzofuran-5-yl)-3-isopropylurea [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: iron; ammonium chloride / ethanol; water / 1 h / 65 °C / Inert atmosphere 2: triethylamine / dichloromethane / 12 h / 0 - 20 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: ammonium chloride; iron / water; ethanol / 1 h / 65 °C 2: triethylamine / dichloromethane / 12 h / 0 - 20 °C
  • 48
  • [ 141645-23-0 ]
  • 1-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)benzofuran-5-yl)-3-propylurea [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: iron; ammonium chloride / ethanol; water / 1 h / 65 °C / Inert atmosphere 2: triethylamine / dichloromethane / 12 h / 0 - 20 °C / Inert atmosphere
  • 49
  • [ 141645-23-0 ]
  • N'-(2-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)benzofuran-5-yl))-N-methylsulfamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: iron; ammonium chloride / ethanol; water / 1 h / 65 °C / Inert atmosphere 2: triethylamine / 5,5-dimethyl-1,3-cyclohexadiene / 2 h / 60 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: ammonium chloride; iron / water; ethanol / 1 h / 65 °C 2: triethylamine / 5,5-dimethyl-1,3-cyclohexadiene / 2 h / 60 °C
  • 50
  • C32H49NO2 [ No CAS ]
  • [ 141645-23-0 ]
YieldReaction ConditionsOperation in experiment
80% With palladium diacetate; triphenylphosphine; silver carbonate In acetonitrile at 115℃; for 15h; Inert atmosphere;
Same Skeleton Products
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