[ CAS No. 3468-18-6 ] {[proInfo.proName]}

Name: 3468-18-6|(1H-Indol-4-yl)methanamine|95%
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SKU: A193103
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Quality Control of [ 3468-18-6 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 3468-18-6 ]

SDS Specification

Alternatived Products of [ 3468-18-6 ]

Product Details of [ 3468-18-6 ]

CAS No. :	3468-18-6	MDL No. :	MFCD04973297
Formula :	C₉H₁₀N₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	FFBWKPKOXRMLNP-UHFFFAOYSA-N
M.W :	146.19	Pubchem ID :	280302
Synonyms :

Calculated chemistry of [ 3468-18-6 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.11
Num. rotatable bonds :	1
Num. H-bond acceptors :	1.0
Num. H-bond donors :	2.0
Molar Refractivity :	45.97
TPSA :	41.81 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.55 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.25
Log Po/w (XLOGP3) :	0.91
Log Po/w (WLOGP) :	1.47
Log Po/w (MLOGP) :	0.96
Log Po/w (SILICOS-IT) :	2.14
Consensus Log Po/w :	1.35

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.86
Solubility :	2.02 mg/ml ; 0.0138 mol/l
Class :	Very soluble
Log S (Ali) :	-1.37
Solubility :	6.19 mg/ml ; 0.0423 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-3.31
Solubility :	0.0721 mg/ml ; 0.000493 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.17

Safety of [ 3468-18-6 ]

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 [ 3468-18-6 ]

* 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 [ 3468-18-6 ]
Downstream synthetic route of [ 3468-18-6 ]

[ 3468-18-6 ] Synthesis Path-Upstream 1~3

1
[ 16136-52-0 ]
[ 3468-18-6 ]

Yield	Reaction Conditions	Operation in experiment
94%	Stage #1: With lithium aluminium tetrahydride In tetrahydrofuran at 20℃; for 0.5 h; Reflux Stage #2: With sodium hydroxide In tetrahydrofuran	Preparation of C-(1H-indol-4-yl)-methylamine To a solution of 4-cyanoindole (7.5 g, 53 mmol) in THF (100 ml) was added at rt a 1.0M solution of lithium aluminum hydride in THF (100 ml, 100 mmol). The mixture was refluxed for 30 min then cooled to rt. The reaction mixture was quenched with 1N NaOH and filtered. The filtrate was acidified with 1N HCl and stirred at rt for 10 min. The pH was adjusted to ~8 by adding sat NaHCO₃ and extracted with n-butanol. The layers were separated and the organic layer was concentrated to dryness. The residue was triturated with methanol. Insoluble materials were removed by filtration and the filtrate was concentrated under reduced pressure to afford the desired product as a solid that was further dried under high vacuum at 50° C. (7.27 g, 94percent yield).
82%	With palladium 10% on activated carbon; hydrogen In methanol at 20℃; Inert atmosphere	Method B. 4-cynoindole (1.0 mmol) was dissolved in MeOH in a hydrogenator reaction flask, 10percent Pd/C (10 mg) was added and hydrogenator was shook at 40-42 psi overnight. Reaction mixture was carefully taken out from hydrogenator, filtered through celite and purified by column chromatography (EtOAc: MeOH; 9.5: 0.5) with few drops of aqueous ammonia.

Reference： [1] Journal of Medicinal Chemistry, 2010, vol. 53, # 6, p. 2646 - 2650
[2] Patent: US2012/238569, 2012, A1, . Location in patent: Page/Page column 29
[3] European Journal of Medicinal Chemistry, 2017, vol. 134, p. 13 - 23
[4] Catalysis Science and Technology, 2014, vol. 4, # 3, p. 629 - 632

2
[ 1074-86-8 ]
[ 3468-18-6 ]

Yield	Reaction Conditions	Operation in experiment
88%	With sodium borohydrid; methylamine In methanol; water	Step C: To a solution of aldehyde product from Step B (2.0 g, 14 mmol) in methanol (100 mL), 40percent methylamine in water (2.27 mL, 27.6 mmol) was added at room temperature over a period of 10 min. The mixture was stirred at room temperature under nitrogen overnight and then was cooled down to 0° C. Sodium borohydride (1.05 g, 27.6 mmol) was added. The reaction mixture was slowly warmed to room temperature for 2 h. Most of methanol was removed in vacuo, and the residue was diluted with water and extracted (3) with ether. The combined organic layers were extracted with 2 N HCl (100 mL). The HCl layer was made basic (pH~11) with 2 N NaOH and extracted (3) with methylene chloride. The combined organic layers were washed with brine, dried over Na₂SO₄, and concentrated in vacuo to give crude 4-(aminomethyl)-indole as a white powder (1.95 g, 88percent): ¹H NMR (300 MHz, CDCl₃) δ 8.29 (s, br, 1H), 7.31 (d, J=8.0 Hz, 1H), 7.22 (t, J=2.7 Hz, 1H), 7.16 (t, J=8.0, 7.3 Hz, 1H), 7.08 (d, J=7.3 Hz, 1H), 6.64 (t, J=2.0 Hz, 1H), 4.06 (s, 2H), 2.51 (s, 3H); CI MS m/z=160 [C₁₀H₁₂N₂+H]⁺.

Reference： [1] Patent: US2002/91134, 2002, A1,

3
[ 16136-52-0 ]
[ 144-55-8 ]
[ 3468-18-6 ]

Yield	Reaction Conditions	Operation in experiment
80%	With sodium hydroxide In tetrahydrofuran	Example 10 Preparation of 1H-indole-4-methanamine Lithium aluminum hydride (3.80 g, 100.0 mmol) was added in 0.5 g portions over 30 min to a solution of 1H-indole-4-carbonitrile (prepared according to Clark, Robin D.; Repke, David B. J. Heterocycl. Chem. 1985, 22, 121-5; 7.50 g, 52.8 mmol) in tetrahydrofuran (250 mL). The mixture was heated at reflux for 30 min. A solution of 1 M sodium hydroxide was added to quench excess lithium aluminum hydride. The mixture was filtered and the filter cake was washed with water. The filtrate was first made acidic with 1 N HCl and then made basic again by the addition of saturated aqueous NaHCO₃. The water layer was then extracted with nBuOH. Evaporation of nBuOH, and drying under vacuum gave 1H-indole-4-methanamine (6.24 g, 80percent) as a beige solid.

Reference： [1] Patent: US6331640, 2001, B1,

[ 3468-18-6 ] Synthesis Path-Downstream 1~57

1
[ 98-03-3 ]
[ 3468-18-6 ]
[ 53462-74-1 ]

Reference： [1]Journal of Medicinal Chemistry,1974,vol. 17,p. 1140 - 1145

3
[ 3468-18-6 ]
[ 647828-37-3 ]
[6-(4-ethoxy-phenyl)-4,5,7-trimethyl-6H-pyrrolo[3,4-d]pyridazin-1-yl]-(1H-indol-4-ylmethyl)-amine [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 746 - 749

4
[ 1074-86-8 ]
[ 3468-18-6 ]

Yield	Reaction Conditions	Operation in experiment
88%	With sodium borohydrid; methylamine; In methanol; water;	Step C: To a solution of aldehyde product from Step B (2.0 g, 14 mmol) in methanol (100 mL), 40% methylamine in water (2.27 mL, 27.6 mmol) was added at room temperature over a period of 10 min. The mixture was stirred at room temperature under nitrogen overnight and then was cooled down to 0 C. Sodium borohydride (1.05 g, 27.6 mmol) was added. The reaction mixture was slowly warmed to room temperature for 2 h. Most of methanol was removed in vacuo, and the residue was diluted with water and extracted (3) with ether. The combined organic layers were extracted with 2 N HCl (100 mL). The HCl layer was made basic (pH~11) with 2 N NaOH and extracted (3) with methylene chloride. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo to give crude 4-(aminomethyl)-indole as a white powder (1.95 g, 88%): 1H NMR (300 MHz, CDCl3) delta 8.29 (s, br, 1H), 7.31 (d, J=8.0 Hz, 1H), 7.22 (t, J=2.7 Hz, 1H), 7.16 (t, J=8.0, 7.3 Hz, 1H), 7.08 (d, J=7.3 Hz, 1H), 6.64 (t, J=2.0 Hz, 1H), 4.06 (s, 2H), 2.51 (s, 3H); CI MS m/z=160 [C10H12N2+H]+.

Reference： [1]Patent: US2002/91134,2002,A1

5
[ 16136-52-0 ]
[ 144-55-8 ]
[ 3468-18-6 ]

Yield	Reaction Conditions	Operation in experiment
80%	With sodium hydroxide; In tetrahydrofuran;	Example 10 Preparation of 1H-indole-4-methanamine Lithium aluminum hydride (3.80 g, 100.0 mmol) was added in 0.5 g portions over 30 min to a solution of 1H-indole-4-carbonitrile (prepared according to Clark, Robin D.; Repke, David B. J. Heterocycl. Chem. 1985, 22, 121-5; 7.50 g, 52.8 mmol) in tetrahydrofuran (250 mL). The mixture was heated at reflux for 30 min. A solution of 1 M sodium hydroxide was added to quench excess lithium aluminum hydride. The mixture was filtered and the filter cake was washed with water. The filtrate was first made acidic with 1 N HCl and then made basic again by the addition of saturated aqueous NaHCO3. The water layer was then extracted with nBuOH. Evaporation of nBuOH, and drying under vacuum gave 1H-indole-4-methanamine (6.24 g, 80%) as a beige solid.

Reference： [1]Patent: US6331640,2001,B1

6
[ 16136-52-0 ]
[ 3468-18-6 ]

Yield	Reaction Conditions	Operation in experiment
94%		Preparation of C-(1H-indol-4-yl)-methylamine To a solution of 4-cyanoindole (7.5 g, 53 mmol) in THF (100 ml) was added at rt a 1.0M solution of lithium aluminum hydride in THF (100 ml, 100 mmol). The mixture was refluxed for 30 min then cooled to rt. The reaction mixture was quenched with 1N NaOH and filtered. The filtrate was acidified with 1N HCl and stirred at rt for 10 min. The pH was adjusted to ~8 by adding sat NaHCO3 and extracted with n-butanol. The layers were separated and the organic layer was concentrated to dryness. The residue was triturated with methanol. Insoluble materials were removed by filtration and the filtrate was concentrated under reduced pressure to afford the desired product as a solid that was further dried under high vacuum at 50 C. (7.27 g, 94% yield).
82%	With palladium 10% on activated carbon; hydrogen; In methanol; at 20℃; under 2068.65 - 2172.08 Torr;Inert atmosphere;	Method B. 4-cynoindole (1.0 mmol) was dissolved in MeOH in a hydrogenator reaction flask, 10% Pd/C (10 mg) was added and hydrogenator was shook at 40-42 psi overnight. Reaction mixture was carefully taken out from hydrogenator, filtered through celite and purified by column chromatography (EtOAc: MeOH; 9.5: 0.5) with few drops of aqueous ammonia.

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 2646 - 2650
[2]Patent: US2012/238569,2012,A1 .Location in patent: Page/Page column 29
[3]Chemical Science,2018,vol. 9,p. 8553 - 8560
[4]European Journal of Medicinal Chemistry,2017,vol. 134,p. 13 - 23
[5]Catalysis science and technology,2014,vol. 4,p. 629 - 632

7
[ 22901-09-3 ]
[ 3468-18-6 ]
[ 1217181-05-9 ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 2646 - 2650

8
[ 1158519-17-5 ]
[ 3468-18-6 ]
[ 1373945-72-2 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 2610 - 2613

9
[ 1158519-18-6 ]
[ 3468-18-6 ]
[ 1373945-74-4 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 2610 - 2613

10
[ 1373945-13-1 ]
[ 3468-18-6 ]
[ 1373945-62-0 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 2610 - 2613

11
[ 1373945-16-4 ]
[ 3468-18-6 ]
[ 1373945-64-2 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 2610 - 2613

12
[ 1373945-18-6 ]
[ 3468-18-6 ]
C₂₂H₁₆F₂N₄O [ No CAS ]
[ 1373945-66-4 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 2610 - 2613

13
[ 1373945-22-2 ]
[ 3468-18-6 ]
[ 1373945-68-6 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 2610 - 2613

14
[ 1373946-77-0 ]
[ 3468-18-6 ]
[ 1373945-70-0 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 2610 - 2613

15
[ 1373945-36-8 ]
[ 3468-18-6 ]
[ 1373945-76-6 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 2610 - 2613

16
[ 3468-18-6 ]
[ 1400661-83-7 ]