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[ CAS No. 289483-69-8 ] {[proInfo.proName]}

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Chemical Structure| 289483-69-8
Chemical Structure| 289483-69-8
Structure of 289483-69-8 * Storage: {[proInfo.prStorage]}
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Product Details of [ 289483-69-8 ]

CAS No. :289483-69-8 MDL No. :MFCD09833234
Formula : C17H12N4O2S Boiling Point : -
Linear Structure Formula :- InChI Key :LWGUASZLXHYWIV-UHFFFAOYSA-N
M.W : 336.37 Pubchem ID :196970
Synonyms :
ER68203-00

Calculated chemistry of [ 289483-69-8 ]

Physicochemical Properties

Num. heavy atoms : 24
Num. arom. heavy atoms : 15
Fraction Csp3 : 0.06
Num. rotatable bonds : 3
Num. H-bond acceptors : 4.0
Num. H-bond donors : 2.0
Molar Refractivity : 89.81
TPSA : 117.92 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : No
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -6.67 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.37
Log Po/w (XLOGP3) : 2.37
Log Po/w (WLOGP) : 3.91
Log Po/w (MLOGP) : 0.56
Log Po/w (SILICOS-IT) : 2.61
Consensus Log Po/w : 2.16

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -3.68
Solubility : 0.0698 mg/ml ; 0.000207 mol/l
Class : Soluble
Log S (Ali) : -4.49
Solubility : 0.011 mg/ml ; 0.0000326 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -6.31
Solubility : 0.000166 mg/ml ; 0.000000494 mol/l
Class : Poorly soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 2.86

Safety of [ 289483-69-8 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 289483-69-8 ]

* 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 [ 289483-69-8 ]

[ 289483-69-8 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 289483-87-0 ]
  • [ 56542-67-7 ]
  • N-(3-cyano-4-methyl-1H-indole-7-yl)-3-cyanobenzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% After suspending 2.50 kg (14.6 mol) of <strong>[289483-87-0]7-amino-3-cyano-4-methyl-1H-indole</strong> and 3.24 kg (16.06 mol) of 3-cyanobenzenesulfonyl chloride [CAS No.56542-67-7] in 25 L of methyl acetate, 87.5 L of methyl acetate and 37.5 L of water were added thereto. Next, 1.39 kg (17.52 mol) of pyridine was added dropwise and the mixture was stirred for 2 hours. After adding 0.36 L (4.38 mol) of concentrated hydrochloric acid to the reaction mixture, it was subjected to liquid-liquid separation and the organic layer was washed with a mixture of 37.5 L of water and 8.8 L of ethanol. After adding activated carbon to the organic layer and stirring at 50C for 30 minutes, the mixture was filtered and concentrated. To this was added 30 L of isopropyl alcohol, and after re-concentration, 91 L of isopropyl alcohol and 9.1 L of water were added and the mixture was heated to 70C. Dissolution was confirmed after 2 hours, and then clarifying filtration was performed and 11.4 L of isopropyl alcohol and 1.1 L of water were added. The solution was slowly cooled to 7C at 10C/hr (with introduction of seed crystals at 64C), and after stirring overnight at 7C, the crystals were collected by filtration. The crystals were dried at 70C under reduced pressure to give 3.6 kg of the title compound as a white crystalline powder (yield: 73%). The moisture content of the obtained white crystalline powder was measured by the Karl Fischer method to be 0.1%, confirming that the obtained crystals were anhydrate crystals. HPLC analysis also confirmed that the obtained crystals were N-(3-cyano-4-methyl-1H-indol-7-yl)-3-cyanobenzenesulfonamide.(HPLC conditions) Mobile phase: CH3CN/H2O/70% HClO4 = 500/500/1 (v/v/v)Flow rate: 1.0 ml/minDetection: UV (282 nm)Column: YMC-Pack Pro C 18 250 x 4.6 mmColumn temperature: 25CRetention time: 8.3 min A powder X-ray diffraction pattern for the obtained crystals is shown in Fig. 3, and the diffraction angle (2theta) peak and peak intensity are shown in Table 7. [Table 7] 2 theta (degree) Relative Intensity 11.4 47 13.0 24 14.4 20 15.2 21 16.4 30 17.0 16 19.1 100 19.8 36 20.4 12 20.9 15 22.6 37 24.0 25 24.5 28 25.0 27 25.6 19 26.3 35 26.8 23 28.8 35 31.6 24 32.7 10 A 13C solid-state NMR spectrum for the obtained crystals is shown in Fig. 5, and the chemical shifts are listed in Table 8. [Table 8] Chemical Shift (ppm) 143.4 137.7 136.9 134.2 131.1 128.5 126.4 125.8 124.3 120.0 118.8 115.8 111.0 84.5 19.4 An infrared spectrum (KBr) for the obtained crystals is shown in Fig. 7, and the wavenumbers (cm-1) and transmittances (%T) of the absorption peak are shown in Table 9. [Table 9] Wavenumber (cm-1) %TWavenumber (cm-1) %T 3212 5 1087 23 2954 26 1060 38 2872 26 984 25 2242 22 939 41 2223 7 905 25 1715 47 839 45 1617 49 819 38 1519 29 795 32 1472 42 754 33 1443 12 690 19 1410 20 676 16 1337 12 652 26 1316 17 625 24 1260 32 607 28 1207 33 588 20 1178 32 559 17 1158 6 518 14 1102 32 420 45
47% Crystals of the title compound were synthesized using the same reaction conditions and recrystallization conditions as for the N-(3-cyano-4-methyl-1H-indol-7-yl)-3-cyanobenzenesulfonamide described in WO00/50359. To a solution of <strong>[289483-87-0]7-amino-3-cyano-4-methyl-1H-indole</strong> (10 g, 58.4 mmol) in tetrahydrofuran (200 ml) were added pyridine (20 ml) and 3-cyanobenzenesulfonyl chloride (12.5 g), followed by stirring at room temperature for 3.5 hours. After further adding 2N hydrochloric acid (100 ml), extraction was performed with ethyl acetate. The organic layer was washed with water (twice) and brine in that order, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate = 2:1-3:2). A mixed solvent of ethanol-hexane (1:2) was added thereto, and after sonication, the precipitate was collected by filtration and washed with a mixed solvent of ethanol-hexane (1:3). The mixture was dried overnight under reduced pressure to give the title compound (9.33 g, 27.7 mmol, 47% yield). 1H-NMR spectrum (DMSO-d6) delta (ppm): 2.58 (3H, s), 6.52 (1H, d, J=7.6Hz), 6.80 (1H, d, J=7.6Hz), 7.74 (1H, m), 7.92 (1H, d, J=8.0Hz), 8.12 (2H, m), 8.19 (1H, d, J=3.2Hz), 10.13 (1H, s), 12.03 (1H, s). A powder X-ray diffraction pattern for the obtained crystals is shown in Fig. 2, and the diffraction angle (2theta) peak and peak intensity are shown in Table 6. [Table 6] PEAK No. 2 theta HALF WIDTH d-VALUE INTENSITY RELATIVE INTENSITY 1 5.960 0.235 14.8167 3492 49 2 8.100 0.212 10.9063 2820 40 3 8.440 0.188 10.4677 1968 28 4 11.920. 0.259 7.4184 4067 57 5 14.120 0.282 6.2671 7103 100 6 15.120 0.259 5.8548 2142 30 7 16.400 0.165 5.4006 2330 33 8 17.660 0.141 5.0180 1905 27 9 17.960 0.212 4.9349 1998 28 10 19.240 0.306 4.6093 5707 80 11 21.380 0.235 4.1526 2443 34 12 21.940 0.282 4.0478 5502 77 13 23.020 0.212 3.8603 2602 37 14 23.580 0.165 3.7699 3172 45 15 23.900 0.400 3.7201 3958 56 16 24.540 0.282 3.6245 2812 40 17 25.840 0.165 3.4451 4302 61 18 26.520 0.212 3.3582 3045 43 19 27.540 0.376 3.2361 3265 46 20 28.380 0.118 3.1422 2655 37 21 28.520 0.188 3.1271 2435 34 It was attempted to produce identical crystals by the same process as Example 1B, but the powder X-ray diffraction pattern did not match. In other words, the crystals obtained in Example 1B were presumably not of a single crystal form but were a mixture of multiple crystal forms. Moreover, it is believed that a single crystal form cannot be produced by the process of Example 1B.
To a suspension of 5.0 g (29 mmol) of the <strong>[289483-87-0]7-amino-3-cyano-4-methyl-1H-indole</strong> obtained in Example 2A and 6.48 g (32 mmol) of 3-cyanobenzenesulfonyl chloride [CAS No. 56542-67-7] in 150 mL of methyl acetate, were added 75 mL of water and 2.83 mL (35 mmol) of pyridine, followed by stirring for 2 hours and 40 minutes. After adding 0.73 mL (9 mmol) of concentrated hydrochloric acid to the reaction mixture, liquid-liquid separation was performed and the organic layer was washed with a mixture of 75 mL of water and 17.5 mL of ethanol. Activated carbon was added to the organic layer and the mixture was stirred at 45-50C for 30 minutes, and then filtered and concentrated. To thus obtained crude crystals were added 96 mL of 2-butanol and 24 mL of water for dissolution at 75C, and the solution was cooled to 7C at approximately 10C/hr and stirred overnight. The precipitated crystals were collected by filtration and washed twice with 10 mL of 2-butanol to give 8.17 g (wet weight) of crystals of the title compound. The crystals were dried under reduced pressure at 70C for 2 hours to give 7.54 g of crystals of the title compound. HPLC analysis confirmed that the obtained compound was identical to the N-(3-cyano-4-methyl-1H-indol-7-yl)-3-cyanobenzenesulfonamide described in WO00/50395.(HPLC conditions) Mobile phase: CH3CN/H2O/70% HClO4 = 500/500/1 (v/v/v)Flow rate: 1.0 mL/minDetection: UV (282 nm)Column: YMC-Pack Pro C18 250 x 4.6 mm A powder X-ray diffraction pattern for the obtained crystals is shown in Fig. 1, and the diffraction angle (2theta) peak and peak intensity are shown in Table 5. [Table 5] PEAK No. 2 theta INTERPLANAR SPACING INTENSITY HALF WIDTH I/Io 1 11.420 7.74203 2122 0.210 55 2 13.040 6.78363 913 0.210 24 3 14. 380 6.15437 778 0.300 20 4 15.200 5.824I5 717 0.210 19 5 15. 540 5.69748 220 0.210 6 6 16.380 5.40714 1013 0.210 26 7 17.000 5. 21131 960 0.210 25 8 19.080 4.64763 3925 0.240 100 9 19.440 4.56237 505 0.150 13 10 19.780 4.48471 1512 0.240 39 11 20.360 4. 35824 470 0.210 12 12 20.900 4.24684 543 0.210 14 13 22.500 3. 94833 1295 0.150 33 14 22.620 3.92765 1437 0.270 37 15 23.160 3.83728 295 0.124 8 16 23.960 3.71094 920 0.330 24 17 24.400 3.64501 890 0.180 23 18 24.520 3.62744 952 0.150 25 19 24.980 3.56168 917 0.240 24 20 25.560 3.48216 693 0.210 18 21 26.260 3.39090 1230 0.270 32 22 26.760 3.32867 823 0.240 21 23 28.840 3.09315 1277 0.210 33 24 29.620 3.01345 270 0.180 7
With pyridine; hydrogenchloride; In tetrahydrofuran; Example 1 3-Cyano-N-(3-cyano-4-methyl-1H-indole-7-yl)benzenesulfonamide The compound (2.00 g, 11.7 mmol) of Production Example 12 was dissolved in 60 ml of tetrahydrofuran, and then 4.0 ml (49.5 mmol) of pyridine and 2.60 g (12.9 mmol) of the compound of Production Example 13 were added thereto. After stirring at room temperature for 16 hr, a 2N hydrochloric acid was added thereto to adjust to pH 1-2, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine successively, dried over magnesium sulfate and concentrated. Then, the resulting residue was purified by silica gel column chromatography to give 3.90 g of the title compound. m.p.: 220-221 C. (recrystallized from ethanol/n-hexane) 1H-NMR(DMSO-d6) delta (ppm); 2.55(3H,s), 6.50(1H,d,J=8.0 Hz), 6.77(1H,d,J=8.0 Hz), 7.71(1H,t,J=8.0 Hz), 7.90(1H,d,J=8.0 Hz), 8.05-8.13(2H,m), 8.16(1H,s), 10.11(1H,brs), 12.01(1H,brs).
With pyridine; In acetic acid methyl ester; water; for 2.66667h;Product distribution / selectivity; Example 3A; Synthesis of N-(3-cyano-4-methyl-1H-indol-7-yl)-3-cyanobenzenesulfonamide; To a suspension of 5.0 g (29 mmol) of the <strong>[289483-87-0]7-amino-3-cyano-4-methyl-1H-indole</strong> obtained in Example 2A and 6.48 g (32 mmol) of 3-cyanobenzenesulfonyl chloride [CAS No. 56542-67-7] in 150 mL of methyl acetate, were added 75 mL of water and 2.83 mL (35 mmol) of pyridine, followed by stirring for 2 hours and 40 minutes. After adding 0.73 mL (9 mmol) of concentrated hydrochloric acid to the reaction mixture, liquid-liquid separation was performed and the organic layer was washed with a mixture of 75 mL of water and 17.5 mL of ethanol. Activated carbon was added to the organic layer and the mixture was stirred at 45-50 C. for 30 minutes, and then filtered and concentrated. To thus obtained crude crystals were added 96 mL of 2-butanol and 24 mL of water for dissolution at 75 C., and the solution was cooled to 7 C at approximately 10 C./hr and stirred overnight. The precipitated crystals were collected by filtration and washed twice with 10 mL of 2-butanol to give 8.17 g (wet weight) of crystals of the title compound. The crystals were dried under reduced pressure at 70 C. for 2 hours to give 7.54 g of crystals of the title compound. HPLC analysis confirmed that the obtained compound was identical to the N-(3-cyano-4-methyl-1H-indol-7-yl)-3-cyanobenzenesulfonamide described in WO00/50395. (HPLC conditions) Mobile phase: CH3CN/H2O/70% HClO4=500/500/1 (v/v/v) Flow rate: 1.0 mL/min Detection: UV (282 nm) Column: YMC-Pack Pro C18 250×4.6 mm
Reference Example 4A Synthesis of N-(3-cyano-4-methyl-1H-indol-7-yl)-3-cyanobenzenesulfonamide To a suspension of 250 g (1.46 mol) of the <strong>[289483-87-0]7-amino-3-cyano-4-methyl-1H-indole</strong> obtained in Reference Example 3A in 5 L of tetrahydrofuran (20-fold amount), were added 354 mL (4.38 mol) of pyridine and 312 g (1.55 mol) of 3-cyanobenzenesulfonyl chloride, followed by stirring at an internal temperature of 21 to 34 C. Disappearance of the starting materials was confirmed after 30 minutes. To the reaction mixture were added 2925 mL of water (11.7-fold amount), 5 L of ethyl acetate (20-fold amount) and a mixture of 730 mL of concentrated hydrochloric acid and 730 mL of water (total of 5.8-fold amount), and liquid-liquid separation was performed. The organic layer was washed with 2925 mL of water, and then 125 g of activated carbon was added and the mixture was stirred for 1 hour. The mixture was filtered through celite and washed twice with 1 L of ethyl acetate. To the filtrate were added 5 L of water and 100 mL of 1 N solution of sodium hydroxide, 1 L of ethyl acetate was further added and liquid-liquid separation was performed. Next, 6 L of water and 2 L of ethyl acetate were added to the organic layer and liquid-liquid separation was performed. The aqueous layer was re-extracted with 2 L of ethyl acetate, and both organic layers were combined and concentrated under reduced pressure at 50 C., after which 1 L of 2-propanol was added and azeotropic distillation and concentration was carried out to give the title compound (666 g, wet weight).

YieldReaction ConditionsOperation in experiment
A list of specific examples of the sulfonamide derivative or the sulfonic acid ester derivative represented by the general formula (I) or the pharmacologically acceptable salt, or the hydrate thereof is as follows: Compound 1 ... N-(3-Chloro-1H-indol-7-yl)-4-[N-[2-(1-imidazolyl)ethyl]-sulfamoyl]benzenesulfonamide 3-(5-Bromonicotinamido)-N-(3-cyano-1H-indol-7-yl)-benzenesulfonamide N-(3-Chloro-1H-indol-7-yl)-4-[N-(2-thiazolyl)sulfamoyl]-benzenesulfonamide 5-Chloro-N-(3-chloro-1H-indol-7-yl)-4-(5-methyl-3-pyridinesulfonamido)-2-thiophenesulfonamide 3-Cyano-N-(3-cyano-4-methyl-1H-indol-7-yl)-benzenesulfonamide
  • 3
  • [ 289483-87-0 ]
  • N-(3-cyano-4-methyl-1H-indole-7-yl)-3-cyanobenzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine; hydrogenchloride; In tetrahydrofuran; SYNTHETIC EXAMPLE 1 N-(3-Cyano-4-methyl-1H-indole-7-yl)-3-cyanobenzenesulfonamide 2.00 g (11.7 mmol) of the compound of Production Example 12 was dissolved in 60 ml of tetrahydrofuran, followed by adding 4.0 ml (49.5 mmol) of pyridine and 2.60 g (12.9 mmol) of the compound of Production Example 13 thereto. After stirring at room temperature for 16 hours, the mixture was adjusted to pH 1 to 2 by adding 2 N hydrochloric acid and extracted with ethyl acetate. The organic layer was successively washed with water and brine, dried over magnesium sulfate and concentrated. Then, the residue was purified by silica gel chromatography, to give 3.90 g of the title compound. (The compound hereinafter is referred to as Compound A.) Melting point: 220-221 C. (recrystallized from ethanol/n-hexane) 1H-NMR(DMSO-d6) delta (ppm): 2.55 (3H, s), 6.50 (1H, d, J=8.0 Hz) 6.77 (1H, d, J=8.0 Hz), 7.71 (1H, t, J=8.0 Hz), 7.90 (1H, d, J=8.0 Hz), 8.05-8.13 (2H, m), 8.16 (1H, s), 10.11 (1H, br s), 12.01 (1H, br s)
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