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[ CAS No. 289483-82-5 ] {[proInfo.proName]}

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Chemical Structure| 289483-82-5
Chemical Structure| 289483-82-5
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Product Details of [ 289483-82-5 ]

CAS No. :289483-82-5 MDL No. :MFCD17779298
Formula : C10H7N3O2 Boiling Point : -
Linear Structure Formula :- InChI Key :XDNBPEYPQDBCIK-UHFFFAOYSA-N
M.W : 201.18 Pubchem ID :11622527
Synonyms :

Calculated chemistry of [ 289483-82-5 ]

Physicochemical Properties

Num. heavy atoms : 15
Num. arom. heavy atoms : 9
Fraction Csp3 : 0.1
Num. rotatable bonds : 1
Num. H-bond acceptors : 3.0
Num. H-bond donors : 1.0
Molar Refractivity : 56.8
TPSA : 85.4 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.14 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.49
Log Po/w (XLOGP3) : 1.96
Log Po/w (WLOGP) : 2.26
Log Po/w (MLOGP) : 0.09
Log Po/w (SILICOS-IT) : 0.75
Consensus Log Po/w : 1.31

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.7
Solubility : 0.401 mg/ml ; 0.00199 mol/l
Class : Soluble
Log S (Ali) : -3.38
Solubility : 0.0842 mg/ml ; 0.000418 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.14
Solubility : 0.145 mg/ml ; 0.000719 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.08

Safety of [ 289483-82-5 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 289483-82-5 ]

* 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.

  • Upstream synthesis route of [ 289483-82-5 ]
  • Downstream synthetic route of [ 289483-82-5 ]

[ 289483-82-5 ] Synthesis Path-Upstream   1~6

  • 1
  • [ 289483-80-3 ]
  • [ 289483-82-5 ]
YieldReaction ConditionsOperation in experiment
97.6%
Stage #1: at 0℃; for 0.5 h;
Stage #2: at 0 - 60℃; for 2 h;
Stage #3: With hydroxylamine hydrochloride In N,N-dimethyl-formamide at 60 - 80℃; for 0.666667 h;
To 740 mL of dimethylformamide was added 235 mL (2.52 mol) of phosphorous oxychloride at 0°C, followed by stirring at 0°C for 0.5 hour. To the reaction mixture was then added a solution of 370 g (2.10 mol) of 4-methyl-7-nitro-1H-indole (WO00/50395) in dimethylformamide (1110 mL) at 0°C, followed by heating and stirring at 60°C for 2 hours. To the reaction mixture was then added dropwise a solution of 292 g (4.20 mol) of hydroxylamine hydrochloride in dimethylformamide (1850 mL) with keeping the internal temperature below 80°C, followed by heating and stirring at 60°C for 40 minutes. After adding 11.1 L of ice water to the reaction mixture while cooling in an ice bath, the mixture was further stirred overnight. The precipitated crystals were collected by filtration and washed with water. The crystals were suspended in 11.1 L of water, 1N solution of sodium hydroxide was added to the suspension for adjustment to pH 7, and then the crystals were collected by filtration and washed with water to give 412 g of the title compound (yield: 97.6percent). HPLC analysis confirmed that the obtained compound was identical to the 3-cyano-4-methyl-7-nitro-1H-indole described in WO00/50395.(HPLC conditions) Mobile phase: CH3CN/H2O/70percent HClO4 = 500/500/1 (v/v/v)Flow rate: 1.0 mL/minDetection: UV (254 nm)Column: YMC-Pack Pro C18 250 x 4.6 mm
Reference: [1] Patent: EP1666463, 2006, A1, . Location in patent: Page/Page column 9-10
  • 2
  • [ 289483-81-4 ]
  • [ 289483-82-5 ]
YieldReaction ConditionsOperation in experiment
89.7%
Stage #1: With pyridine; hydroxylamine hydrochloride In N,N-dimethyl-formamide at 60℃; for 0.666667 h;
Stage #2: With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide at 0 - 60℃; for 0.5 h;
Stage #3: With triethylamine In N,N-dimethyl-formamide at 60℃; for 1 h;
Reference Example 2A
Synthesis of 3-cyano-4-methyl-7-nitro-1H-indole
After dissolving 2.21 g (10.8 mmol) of the 3-formyl-4-methyl-7-nitro -1H-indole obtained in Reference Example 1A in 100 mL of dimethylformamide, 900 mg (13.0 mmol) of hydroxylamine hydrochloride and 1.05 mL (13.0 mmol) of pyridine were added.
The mixture was heated and stirred at 60° C. for 40 minutes, and then 1,1'-carbonyldiimidazole (53.9 mmol) was added to the reaction mixture while cooling in an ice bath.
The mixture was further heated and stirred at 60° C. for 30 minutes, and then 3.0 mL (21.5 mmol) of triethylamine was added to the reaction mixture, and heating and stirring were continued at the same temperature for 1 hour.
To the reaction mixture was added 50 mL of ice water while cooling in an ice bath and extraction was performed with ethyl acetate.
The organic layer was washed with water and brine in that order, dried over magnesium sulfate, and concentrated to dryness.
A mixture of tert-butyl methyl ether and hexane was added to the residue, and the crystals were collected by filtration to give 1.95 g of the title compound (yield: 89.7percent).
1H-NMR (DMSO-d6) δ (ppm): 2.78 (3H, s), 7.22 (1H, d, J=8.0Hz), 8.14 (1H, d, J=8.0Hz), 8.41 (1H, s), 12.76 (1H, br s).
Reference: [1] Patent: US2007/37854, 2007, A1, . Location in patent: Page/Page column 5-6
  • 3
  • [ 289483-81-4 ]
  • [ 530-62-1 ]
  • [ 289483-82-5 ]
Reference: [1] Patent: US2002/128480, 2002, A1,
[2] Patent: EP1258252, 2002, A1,
[3] Patent: US2004/18192, 2004, A1,
  • 4
  • [ 289483-80-3 ]
  • [ 68-12-2 ]
  • [ 289483-82-5 ]
YieldReaction ConditionsOperation in experiment
97.6%
Stage #1: at 0℃; for 0.5 h;
Stage #2: at 0 - 60℃; for 2 h;
Example 1A; Synthesis of 3-cyano-4-methyl-7-nitro-1H-indole; To 740 mL of dimethylformamide was added 235 mL (2.52 mol) of phosphorous oxychloride at 0° C., followed by stirring at 0° C. for 0.5 hour. To the reaction mixture was then added a solution of 370 g (2.10 mol) of 4-methyl-7-nitro-1H-indole (WO00/50395) in dimethylformamide (1110 mL) at 0° C., followed by heating and stirring at 60° C. for 2 hours. To the reaction mixture was then added dropwise a solution of 292 g (4.20 mol) of hydroxylamine hydrochloride in dimethylformamide (1850 mL) with keeping the internal temperature below 80° C., followed by heating and stirring at 60° C. for 40 minutes. After adding 11.1 L of ice water to the reaction mixture while cooling in an ice bath, the mixture was further stirred overnight. The precipitated crystals were collected by filtration and washed with water. The crystals were suspended in 11.1 L of water, 1 N solution of sodium hydroxide was added to the suspension for adjustment to pH 7, and then the crystals were collected by filtration and washed with water to give 412 g of the title compound (yield: 97.6percent). HPLC analysis confirmed that the obtained compound was identical to the 3-cyano-4-methyl-7-nitro -1H-indole described in W00/50395. (HPLC conditions) Mobile phase: CH3CN/H2O/70percent HClO4=500/500/1 (v/v/v) Flow rate: 1.0 mL/min Detection: UV (254 nm) Column: YMC-Pack Pro C18 250.x.4.6 mm
Reference: [1] Patent: US2007/37854, 2007, A1, . Location in patent: Page/Page column 4
  • 5
  • [ 289483-82-5 ]
  • [ 289483-87-0 ]
YieldReaction ConditionsOperation in experiment
99.8% With hydrogen In tetrahydrofuran; methanol at 20℃; Reference Example 3A; Synthesis of 7-amino-3-cyano-4-methyl-1H-indole; After suspending 12.6 g (62.6 mmol) of the 3-cyano-4-methyl-7-nitro-1H-indole obtained in Reference Example 2A in a mixture of 100 mL of tetrahydrofuran and 100 mL of methanol, the suspension was subjected to hydrogenation in the presence of 430 mg (1.87 mmol) of platinum oxide at ordinary temperature, 3 atmospheres. The catalyst was removed by filtration, the filtrate was concentrated to dryness, and then a mixture of tert-butyl methyl ether and hexane was added to the residue and the crystals were collected by filtration to give 10.7 g of the title compound (yield: 99.8percent). 1H-NMR (DMSO-d6) δ (ppm): 2.47 (3H, s), 5.07 (2H, s), 6.34 (1H, d, J=7.6Hz), 6.64 (1H, d, J=7.6Hz), 8.10 (1H, s), 11.70 (1H, br s).
84.8% With hydrogen In methanol; ethyl acetate at 20℃; After suspending 400 g (1.99 mol) of the 3-cyano-4-methyl-7-nitro-1H-indole obtained in Example 1A in a mixture of 6 L of ethyl acetate and 6 L of methanol, the suspension was subjected to hydrogenation in the presence of 40 g of 10percent palladium-carbon at ordinary temperature, 4 atmospheres. After removing the catalyst by filtration, the filtrate was treated with activated carbon and concentrated to give crude crystals. The crude crystals were dissolved in 6 L of 1,2-dimethoxyethane at an external temperature of 60°C, and then 12 L of water was added dropwise. Upon confirming precipitation of crystals, the mixture was stirred for 1.5 hours while cooling in an ice bath and filtered, and the crystals were washed twice with water (1 L). The crystals were air-dried at 50°C for 16 hours to give 289 g of the title compound (yield: 84.8percent). HPLC analysis confirmed that the obtained compound was identical to the 7-amino-3-cyano-4-methyl-1H-indole described in WO00/50395.(HPLC conditions) Mobile phase: CH3CN/H2O/70percent HClO4 = 400/600/1 (v/v/v)Flow rate: 1.0 mL/minDetection: UV (282 nm)Column: YMC-Pack Pro C18 250 x 4.6 mm
84.8% With hydrogen In methanol; ethyl acetate at 20℃; Example 2A; Synthesis of 7-amino-3-cyano-4-methyl-1H-indole; After suspending 400 g (1.99 mol) of the 3-cyano-4-methyl-7-nitro-1H-indole obtained in Example 1A in a mixture of 6 L of ethyl acetate and 6 L of methanol, the suspension was subjected to hydrogenation in the presence of 40 g of 10percent palladium-carbon at ordinary temperature, 4 atmospheres. After removing the catalyst by filtration, the filtrate was treated with activated carbon and concentrated to give crude crystals. The crude crystals were dissolved in 6 L of 1,2-dimethoxyethane at an external temperature of 60° C., and then 12 L of water was added dropwise. Upon confirming precipitation of crystals, the mixture was stirred for 1.5 hours while cooling in an ice bath and filtered, and the crystals were washed twice with water (1 L). The crystals were air-dried at 50° C. for 16 hours to give 289 g of the title compound (yield: 84.8percent). HPLC analysis confirmed that the obtained compound was identical to the 7-amino-3-cyano-4-methyl-1H-indole described in WO00/50395. (HPLC conditions) Mobile phase: CH3CN/H2O/70percent HClO4=400/600/1 (v/v/v) Flow rate: 1.0 mL/min Detection: UV (282 nm) Column: YMC-Pack Pro C18 250.x.4.6 mm
Reference: [1] Patent: US2007/37854, 2007, A1, . Location in patent: Page/Page column 6
[2] Patent: EP1666463, 2006, A1, . Location in patent: Page/Page column 10
[3] Patent: US2007/37854, 2007, A1, . Location in patent: Page/Page column 4
  • 6
  • [ 289483-82-5 ]
  • [ 289483-86-9 ]
  • [ 289483-87-0 ]
Reference: [1] Patent: EP1258252, 2002, A1,
[2] Patent: US2004/18192, 2004, A1,
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