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Chemical Structure| 5422-44-6 Chemical Structure| 5422-44-6
Chemical Structure| 5422-44-6

1-Methyl-1H-tetrazol-5-amine

CAS No.: 5422-44-6

4.5 *For Research Use Only !

Cat. No.: A659235 Purity: 98%

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Product Details of [ 5422-44-6 ]

CAS No. :5422-44-6
Formula : C2H5N5
M.W : 99.09
SMILES Code : NC1=NN=NN1C
MDL No. :MFCD00186454
InChI Key :GTKOKCQMHAGFSM-UHFFFAOYSA-N
Pubchem ID :138492

Safety of [ 5422-44-6 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H228-H315-H319
Precautionary Statements:P210-P240-P264-P280-P302+P352+P332+P313+P362+P364-P305+P351+P338+P337+P313
Class:4.1
UN#:1325
Packing Group:

Calculated chemistry of [ 5422-44-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 7
Num. arom. heavy atoms 5
Fraction Csp3 0.5
Num. rotatable bonds 0
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 23.48
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

69.62 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

0.56
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

-0.78
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

-1.2
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

-0.89
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-0.51
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.56

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-0.49
Solubility 32.0 mg/ml ; 0.322 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-0.2
Solubility 62.0 mg/ml ; 0.625 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

0.39
Solubility 242.0 mg/ml ; 2.44 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

No
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-7.46 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

2.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

2.05

Application In Synthesis of [ 5422-44-6 ]

* 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.

  • Downstream synthetic route of [ 5422-44-6 ]

[ 5422-44-6 ] Synthesis Path-Downstream   1~12

  • 1
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  • 2
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  • [ 77-78-1 ]
  • [ 6154-04-7 ]
  • [ 5422-44-6 ]
YieldReaction ConditionsOperation in experiment
25%; 51% A solution of sodium hydroxide (20%) was added dropwise to a suspension of 5-aminotetrazole monohydrate (10.3 g; 0.1 mol) in water (30 mL), with a drop of phenolphthalein. The mixture was stirred until complete dissolution of the suspended material. Dimethyl sulfate (20 mL; 0.11 mol) was then added in small portions, keeping an alkaline medium through addition of aqueous sodium hydroxide. The final mixture was refluxed for 1 h, then cooled, and finally left in an ice bath, in the fridge, for 2 days. Colorless needles of the desired compound were filtered (6.1 g; 51% yield), m.p. 220-221 C, 1H NMR (CDCl3): delta 4.15 (3H, s), MS (EI): m/z 99 [M+].
25%; 51% With phenolphthalein; sodium hydroxide; In water; for 1h;Reflux; General procedure: A solution of sodium hydroxide (20%) was added dropwise to a suspension of 5aminotetrazole monohydrate (120 mmol) in water (30 mL), with a drop of phenolphthalein. The mixture was stirred until complete dissolution of the suspended material. Dimethyl sulphate (110 mmol) was then added in small portions, keeping an alkaline medium through addition of aqueous sodium hydroxide. The final mixture was refluxed for 1 h, then cooled, and finally left in ice bath for 48h. Colourless needles of the desired compound were filteredand dried (51% yield).
  • 3
  • [ 4418-61-5 ]
  • [ 74-88-4 ]
  • [ 6154-04-7 ]
  • [ 5422-44-6 ]
YieldReaction ConditionsOperation in experiment
18%; 50% A 500 mL R.B. flask was fitted with a magnetic stirrer andcharged with 30 mL of distilled water and 5-aminotetrazole monohydrate(17, 10.3 g, 0.1 mol), which formed a suspension. The flaskwas fitted with a pressure equalizing addition funnel containing25 mL of 20% NaOH solution (5 g, 0.125 mol). The solution wasadded dropwise to the flask over 0.5 h. A clear solution wasobtained in the flask. Then the pressure equalizing addition funnelwas replaced by another pressure equalizing addition funnel containinga solution of methyl iodide (14.2 g, 6.22 mL, 0.1 mol) in160 mL of acetone. The methyl iodide solution was added dropwiseto the flask over an hour. Afterwords, the reaction solution wasstirred at room temperature for three days and monitored by tlcas it proceeded to completion. During this 72 h period most ofthe acetone evaporated. The reaction solution was transferred to500 mL beaker and left in the hood overnight. A white solidprecipitated (6.6 g), which was spectroscopically identified as95:5 mixture of 1methyl5aminotetrazole ( 18) and 2methyl5aminotetrazole (19). This mixture was recrystallized from an acetone-water mixture yielding pure product 18 (5 g, 0.05 mol,50% yield); m.p. 220 C. TLC (acetonitrile) Rf = 0.65. The originalmother liquor (from which the 6.6 g precipitated) was evaporated,and 150 mL chloroform was added to the remaining white solid(which contained the minor product 19 and the inorganic saltNaI). The slurry was magnetically stirred overnight in order toextract the organic material, and the solid sodium iodide was filtered off. The yellow chloroform was evaporated yielding thedesired product 19. The latter was obtained pure via recrystallizationfrom water (1.8 g, 0.018 mol, 18% yield); M.p. 105 C. TLC (acetonitrile):Rf = 0.55.18: 1H NMR (DMSO-d6): delta 6.66 (s, 2H), 3.70 (s, 3H) ppm. 13CNMR (DMSO-d6): delta 155.71, 32.03 ppm. HRMS (m/z): calcd for[C2H6N5]+ 100.06185, obsd 100.06177.19: 1H NMR (DMSO-d6): delta 5.96 (s, 2H), 4.07(s, 3H) ppm. 13CNMR (DMSO-d6): delta 167.05, 38.68 ppm. HRMS (m/z): calcd for[C2H6N5]+ 100.06181, obsd 100.06177.
With caesium carbonate; In acetonitrile; for 7h;Heating / reflux; A mixture of 5-aminotetrazole (24.4 g, 0.29 mol), methyliodide (48.8 g, 0.34 mol), and Cs2CO3 (112.0 g, 0.34 mol) in acetonitrile (700 mL) is stirred and refluxed for 7 hours. The mixture is cooled to 50 0C and filtrated. The resulting filtrate is concentrated to give a mixture of 5-amino-2-methyltetrazole and 5-amino-1-methyltetrazole.
With caesium carbonate; In acetonitrile; for 7h;Heating / reflux; A mixture of 5-aminotetrazole (24.4 g, 0.29 mol), methyliodide (48.8 g, 0.34 mol), and Cs2CO3 (112.0 g, 0.34 mol) in acetonitrile (700 mL) is stirred and refluxed for 7 hours. The mixture is cooled to 50 0C and filtrated. The resulting filtrate is concentrated to give the mixture of 5-amino-2-methyltetrazole and 5-amino-1-methyltetrazole.
With caesium carbonate; In acetonitrile; for 7h;Heating / reflux; A mixture of 5-aminotetrazole (24.4 g, 0.29 mol), methyliodide (48.8 g, 0.34 mol), and Cs2CO3 (112.0 g, 0.34 mol) in acetonitrile (700 mL) is stirred and refluxed for 7 hours. The mixture is cooled to 50 0C and filtrated. The resulting filtrate is concentrated to give the mixture of 5-amino-2-methyltetrazole and 5-amino-1-methyltetrazole.

  • 4
  • [ 186581-53-3 ]
  • 1<i>H</i>-tetrazol-5-ylamine hydrate [ No CAS ]
  • [ 6154-04-7 ]
  • [ 5422-44-6 ]
  • 5
  • [ 77-78-1 ]
  • 1<i>H</i>-tetrazol-5-ylamine hydrate [ No CAS ]
  • [ 6154-04-7 ]
  • [ 5422-44-6 ]
  • 6
  • [ 4418-61-5 ]
  • MeX [ No CAS ]
  • [ 6154-04-7 ]
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  • 7
  • [ 4418-61-5 ]
  • [ 74-88-4 ]
  • [ 6154-04-7 ]
  • [ 5422-44-6 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate; In acetonitrile; at 50℃; for 18h; Example G: Preparation of N-[3,5-bis(trifluoromethyl)benzyl]-N-(2-methyl-2/-/-tetrazol-5- yl)amine<Method 1> <n="84"/>Step 1 :Methyliodide (45 ml_, , 1.2 eq., 0.72 mol) is added to a mixture of 5-aminotetrazole (51.1g, 0.60 mol) and Cs2CO3 (235.0 g, 1.2 eq., 0.72 mol) in acetonitrile (500 ml_), and the resulting mixture is stirred at 50 0C for 18 hours. The mixture (at 50 0C) is filtered, and the residue is washed with hot acetnitrile (50 0C). The filtrate is concentrated to give the mixture of desired 5-amino-2-methyltetrazole and 5-amino-1-methyltetrazole.
  • 8
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  • [ 401-95-6 ]
  • 2-methyl-N-[3,5-bis(trifluoromethyl)phenylmethylene]-2H-tetrazole-5-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
In toluene; for 5h;Heating / reflux;Product distribution / selectivity; Step 2:A crude mixture of 5-amino-2-methyltetrazole and 5-amino-1-methyltetrazole is treated with 3,5-bis(trifluoromethyl)benzaldehyde (48 ml_, 71g, 0.29 mol) in toluene (780 ml_), and the mixture is stirred and refluxed for 5 hours. The resulting mixture is filtered to remove off the insoluble solid (5-amino-1-methyltetrazole), and the residue is washed with hot toluene. The filtrate is concentrated to give crude 2-methyl-N-[3,5-bis(trifluoromethyl)phenylmethylene]- 2H-tetrazole-5-amine (70.1g).
  • 9
  • [ 949089-83-2 ]
  • [ 949089-95-6 ]
  • [ 6154-04-7 ]
  • [ 5422-44-6 ]
YieldReaction ConditionsOperation in experiment
With hydrogen;palladium dihydroxide; In ethanol; at 50℃; under 2585.81 Torr; for 16h; 2-methyl-2H-tetrazol-5-amineTo a clean stainless steel reactor added palladium hydroxide (1 g), 10 gm of N,N-dibenzyl-2-methyl-2H-tetrazol-5-amine from Step C (10 g) and ethanol (100 mL). The reaction was charged with hydrogen and heated to 50 C. and the pressure was maintained at 50 psi hydrogen for 16 hours. When the uptake of hydrogen had ceased, the reaction was purged with nitrogen and the catalyst removed by filtration. The pad was washed with 25 mL of ethanol and combined with the filtrate and concentrated to an off white solid to give 2.7 gm (73%) of product. An analytical sample was prepared by recrystallization from isopropanol. 1H NMR (400 MHz, DMSO-d6) 5.94 (s 2H), 4.03 (s 3H) 13C NMR (400 MHz, DMSO-d6 167.8, 40.52, C, H, N Calculated (found) 68.79 (68.54), 6.13 (6.41), 25.07 (24.83)Alternatively, employing a mixture of regioisomers: to a clean stainless steel reactor added palladium hydroxide (1.4 g), 14 g of a 9:1 mixture of N,N-dibenzyl-2-methyl-2H-tetrazol-5-amine and N,N-Dibenzyl-1-methyl-1H-tetrazol-5-amine from Step C, and ethanol (140 mL). The reaction was charged with hydrogen and heated to 50 C. and the pressure was maintained at 50 psi hydrogen for 16 hours. When the uptake of hydrogen ceased the reaction was purged with nitrogen and the catalyst removed via filtration. The pad was washed with 50 mL of ethanol and combined with the filtrate and concentrated to an off white solid to give 5.1 gm (quantitative mixture of 1-methyl-2H-tetrazol-5-amine and 2-methyl-2H-tetrazol-5-amine). The crude reaction mixture was taken up in methylene chloride and the undesired isomer filtered away. The methylene chloride layer was displaced with isopropanol to give 3.8 gm of the desired product.
With hydrogen;palladium dihydroxide; In ethanol; at 50℃; under 2585.81 Torr; for 16h; Step D: 2-methyl-2H-tetrazol-5-amineTo a clean stainless steel reactor added palladium hydroxide (1 g), 10 gm of N,N-dibenzyl-2-methyl-2H-tetrazol-5-amine from Step C (10 g) and ethanol (100 mL). The reaction was charged with hydrogen and heated to 50 C. and the pressure was maintained at 50 psi hydrogen for 16 hours. When the uptake of hydrogen had ceased, the reaction was purged with nitrogen and the catalyst removed by filtration. The pad was washed with 25 mL of ethanol and combined with the filtrate and concentrated to an off white solid to give 2.7 gm (73%) of product. An analytical sample was prepared by recrystallization from isopropanol. 1H NMR (400 MHz, DMSO-d6) 5.94 (s 2H), 4.03 (s 3H) 13C NMR (400 MHz, DMSO-d6 delta 167.8, 40.52, C, H, N Calculated (found) 68.79 (68.54), 6.13 (6.41), 25.07 (24.83)Alternatively, employing a mixture of regioisomers: to a clean stainless steel reactor added palladium hydroxide (1.4 g), 14 g of a 9:1 mixture of N,N-dibenzyl-2-methyl-2H-tetrazol-5-amine and N,N-Dibenzyl-1-methyl-1H-tetrazol-5-amine from Step C, and ethanol (140 mL). The reaction was charged with hydrogen and heated to 50 C. and the pressure was maintained at 50 psi hydrogen for 16 hours. When the uptake of hydrogen ceased the reaction was purged with nitrogen and the catalyst removed via filtration. The pad was washed with 50 mL of ethanol and combined with the filtrate and concentrated to an off white solid to give 5.1 gm (quantitative mixture of 1-methyl-2H-tetrazol-5-amine and 2-methyl-2H-tetrazol-5-amine). The crude reaction mixture was taken up in methylene chloride and the undesired isomer filtered away. The methylene chloride layer was displaced with isopropanol to give 3.8 gm of the desired product.
  • 10
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  • [ 669080-86-8 ]
YieldReaction ConditionsOperation in experiment
A mixture of the crude product and 3,5-bis(trifluoromethyl)benzaldehyde (43.0 g, 0.18 mol) in toluene (600 mL) is stirred and refluxed for 45 min. After cooling to room temperature, the resulting mixture is concentrated. NaBH4 (8.12 g, 0.22 mol) is added portionwise slowly to <n="47"/>Case 50508EtOH (500 ml_) solution of the resulting residue, and the mixture is stirred at room temperature for 4 hours. After addition of sat. NH4CI aq. and water, the mixture is extracted with ethyl acetate. The combined organic layer is washed with brine, dried over magnesium sulfate, filtered and concentrated. The crude product is purified by crystallization (50 mL of /- PrOHiH2O. 3:7) to give [3,5-bis(trifluoromethyl)phenylmethyl](2-methyl-2H-tetrazol-5- yl)amine.
A mixture of the crude product and 3,5-bis(trifluoromethyl)benzaldehyde (43.0 g, 0.18 mol) in toluene (600 mL) is stirred and refluxed for 45 min. After cooling to room temperature, the resulting mixture is concentrated. NaBH4 (8.12 g, 0.22 mol) is added portionwise slowly to EtOH (500 mL) solution of the resulting residue, and the mixture is stirred at room temperature for 4 hours. After addition of sat. NH4CI aq. and water, the mixture is extracted with ethyl acetate. The combined organic layer is washed with brine, dried over magnesium sulfate, filtered and concentrated. The crude product is purified by crystallization (50 mL of /- PrOH:H2O. 3:7) to give [3,5-bis(trifluoromethyl)phenylmethyl](2-methyl-2tf-tetrazol-5- yl)amine .
  • 11
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  • [ 5422-44-6 ]
  • 12
  • [ 15454-54-3 ]
  • [ 77-78-1 ]
  • [ 6154-04-7 ]
  • [ 5422-44-6 ]
YieldReaction ConditionsOperation in experiment
25%; 51% With phenolphthalein; sodium hydroxide; In water; for 1h;Reflux; The tetrazolyl derivative 4a was prepared from commerciallyavailable 5-aminotetrazole monohydrate through methylation.This reaction produces a mixture of 1-methyl-(1H)-tetrazole-5-amine and 2-methyl-(2H)-tetrazole-5-amine. The isomers havedifferent solubility and are separated during work-up, as described.A solution of sodium hydroxide (20% w/v) was added drop-wise to a suspension of 5-aminotetrazole monohydrate (10.3 g;0.1 mol) in water (30 mL), with a drop of phenolphthalein. Themixture was stirred until complete dissolution of the suspendedmaterial. Dimethyl sulfate (20 mL; 0.11 mol) was then added insmall portions, keeping an alkaline medium through addition ofaqueous sodium hydroxide. The final mixture was refluxed for 1 h,then cooled, and finally left in an ice bath, in the fridge, for 2 days.Colorless needles of 1-methyl-(1H)-tetrazole-5-amine (4b) were separated by filtration (6.1 g; 51% yield); m.p. 220-221C;1H NMR(CDCl3): d 4.15 (3H, s); MS (EI): m/z 99 [M+]. The filtrate collected was evaporated under reduced pressureto afford a solid residue. Water (50 mL) was added, and the mix-ture was then extracted with diethyl ether (3 × 50 mL). The organicextract was dried over anhydrous sodium sulfate, filtered and thefiltrate evaporated to afford white crystals. Recrystallization fromdiethyl ether gave 2-methyl-(2H)-tetrazole-5-amine (4a) as col-orless needles; (3.0 g, 25% yield); m.p. 104.5-105.5C;1H NMR(CDCl3): d 3.32 (3H, s); MS (EI): m/z 99 [M+].
 

Historical Records

Technical Information

Categories

Related Functional Groups of
[ 5422-44-6 ]

Amines

Chemical Structure| 13183-79-4

A674247 [13183-79-4]

5-Mercapto-1-methyltetrazole

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Related Parent Nucleus of
[ 5422-44-6 ]

Tetrazoles

Chemical Structure| 13183-79-4

A674247 [13183-79-4]

5-Mercapto-1-methyltetrazole

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