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Chemical Structure| 38603-72-4 Chemical Structure| 38603-72-4

Structure of Cimetidine Impurity J
CAS No.: 38603-72-4

Chemical Structure| 38603-72-4

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Product Details of [ 38603-72-4 ]

CAS No. :38603-72-4
Formula : C7H15Cl2N3S
M.W : 244.19
SMILES Code : NCCSCC1=C(C)N=CN1.[H]Cl.[H]Cl
MDL No. :MFCD12031495
InChI Key :VFWUYASTZCOUKN-UHFFFAOYSA-N
Pubchem ID :3015999

Safety of [ 38603-72-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 38603-72-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 5
Fraction Csp3 0.57
Num. rotatable bonds 4
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 62.36
TPSA ?

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

80.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

1.42
Log Po/w (WLOGP)?

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

2.36
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.

0.44
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

1.69
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.18

Water Solubility

Log S (ESOL):?

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

-2.27
Solubility 1.31 mg/ml ; 0.00538 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-2.7
Solubility 0.482 mg/ml ; 0.00197 mol/l
Class?

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

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

-2.58
Solubility 0.638 mg/ml ; 0.00261 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

Yes
Log Kp (skin permeation)?

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

-6.78 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

0.0
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)

2.75

Application In Synthesis of [ 38603-72-4 ]

* 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 [ 38603-72-4 ]

[ 38603-72-4 ] Synthesis Path-Downstream   1~15

YieldReaction ConditionsOperation in experiment
98.1% EXAMPLE 10 4-Methyl-5-[(2-aminoethyl)-thiomethyl]-imidazole dihydrochloride 108 g of 4-methyl-5-hydroxymethylimidazole hydrochloride (=20 mole % excess) and 72 g of 2,2-dimethylthiazolidine are introduced into 1,350 ml of concentrated hydrochloric acid, whilst cooling to 20-30 C. The mixture is refluxed for 17 hours and then evaporated to dryness under reduced pressure. The residue obtained (235 g) is recrystallized from 400 ml of alcohol. 144 g of 4-methyl-5-[(2-aminoethyl)-thiomethyl]-imidazole dihydrochloride (corresponding to a yield of 98.1% of theory), of melting point 185-192.5 C., are obtained.
84.0% EXAMPLE 8 4-Methyl-5-[(2-aminoethyl)-thiomethyl]-imidazole dihydrochloride 30 g of 4-methyl-5-hydroxymethylimidazole hydrochloride and 23 g of cysteamine in 450 ml of concentrated hydrochloric acid are refluxed for 17 hours. The solution is evaporated to dryness under reduced pressure. The residue (61 g) is recrystallized from 500 ml of alcohol. 41 g of 4-methyl-5-[(2-aminoethyl)-thiomethyl]imidazole dihydrochloride (corresponding to a yield of 84.0% of theory), of melting point 184-191 C., are obtained.
49% EXAMPLE 4 Preparation of 4-methyl-5-(2-aminoethyl)-thio-methylimidazole dihydrochloride A mixture containing cysteamine hydrochloride (18.75 g, 0.165 mol),-4-hydroxymethyl-5-methylimidazole hydrochloride (25 g, 0.169 mol), concentrated hydrochloric acid (10 mL) and isopropanol (17 mL) is heated to 70-80 C. The solvent is removed under reduced pressure and the crude product is pulped with n-butanol. The precipitate is filtered and dried to give 19.7 g of the expected product (49%).
Five hundred and eighty two (582) g of this aqueous solution was concentrated and thrown into 1,000 g of 1-propanol. The precipitate consequently produced was separated by filtration and then dried, to afford 162 g of white crystals of 4-methyl-5-[(2-aminoethyl)-thiomethyl]-imidazole dihydrochloride.
One hundred (100) g of this aqueous solution was concentrated and thrown into 150 g of 1-propanol. The precipitate consequently produced was separated by filtration and then dried, to afford 19 g of white crystals of 4-methyl-5-[(2-aminoethyl)-thiomethyl]-imidazole dihydrochloride.
At the same time, 2,640 g of a liquid containing 74 g of 4-methyl-5-[(2-aminoethyl)-thiomethyl]-imidazole hydrochloride, and other unaltered reactants and hydrochloric acid was obtained as the outer liquid. The inner liquis thus obtained was concentrated under a vacuum and thrown into 1-propanol. The crystals consequently precipitated were separated by filtration and dried, to produce 159 g of white crystals of 4-methyl-5-[(2-aminoethyl)-thiomethyl]-imidazole dihydrochloride

  • 2
  • [ 23187-14-6 ]
  • [ 38603-72-4 ]
YieldReaction ConditionsOperation in experiment
Separately, the outer liquid obtained in the electrodialytic device 10 was withdrawn at a flow rate of 336.3 g/min. through a conduit 13 and supplied to a concentrator 14 and concentrated therein, to prepare a liquid containing 5.2% by weight of 4-methyl-5-[(2-aminoethyl)-thiomethyl]-imidazole dihydrochloride, 8.4% by weight of 4-methylimidazole hydrochloride, and the balance of unaltered reactants and hydrochloric acid. This liquid was returned at a flow rate of 141 g/min. through a conduit 15 to the reactor 6.
  • 3
  • N-cyano-2-imino-4-methyl-1,3-dithian [ No CAS ]
  • [ 38603-72-4 ]
  • [ 76181-71-0 ]
YieldReaction ConditionsOperation in experiment
73% With sodium hydroxide; methylamine; In methanol; nitrogen; Detection: UV (229 nm) EXAMPLE 3 4-Methyl-5-[(2-aminoethyl)thiomethyl]imidazole dihydrochloride 24.4 g (0.10 mole), N-cyano-2-imino-4-methyl-1,3-dithian 15.5 g (0.09 mole) and methanol 500 ml were placed in a reaction flask, 160 g of 5% methanolic solution of sodium hydroxide was added dropwise with stirring at a temperature in the range of 30 to 35 C. over a period of three hours while slowly flowing nitrogen gas, and stirring was continued at that temperature for an additional three hours. After making sure that the 1,3-dithian compound had been consumed almost completely, 78 g (1.0 mole) of 40% methanolic solution of methylamine was added, and the reaction was continued at 25 to 30 C. for 24 hours. Analysis of the reaction mixture thus obtained by liquid chromatography showed the formation of N-cyano-N'-methyl-N"[2-((4-methyl-5-imidazolyl)methylthio)ethyl]guanidine with a yield of 73%.
  • 4
  • [ 79667-58-6 ]
  • [ 38603-72-4 ]
  • [ 79667-63-3 ]
YieldReaction ConditionsOperation in experiment
With ammonia; triethylamine; In tetrahydrofuran; methanol; chloroform; ethyl acetate; acetone; EXAMPLE 63 A mixture of 4-methyl-5-[(2-aminoethyl)thiomethyl]imidazole dihydrochloride (0.5 g.), triethylamine (1 ml.) and 2-[2-(2,2,2-trifluoroethyl)guanidino]-(4-isothiocyanatobutyl)thiazole (0.5 g.) in tetrahydrofuran (15 ml.) was allowed to stand at room temperature overnight. The solution then was filtered, and the filtrate evaporated to dryness. The residue was purified by preparative thin layer chromatography using ethyl acetate/methanol/ammonia 6:1:1 v/v/v as developing solvent. The appropriate band was isolated and further purified by preparative thin layer chromatography using methanol/chloroform/ammonia 15:85:1 v/v/v as developing solvent. The appropriate band after extraction and evaporation yielded a brown gum. This was treated in acetone with excess maleic acid to give 1-[4-(2-[2-(2,2,2-trifluoroethyl)-guanidino]thiazol-4-yl)butyl]-3-[2-([4-methylimidazol-5-yl]methylthio)ethyl]thiourea containing 2.25 equivalents of maleic acid.
  • 5
  • [ 38603-72-4 ]
  • [ 556-61-6 ]
  • N-methyl-N'-[2-((4-methyl-5-imidazolyl)methylthio)ethyl]thiourea [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In water; b. i. Potassium carbonate (7.75 g.) was added to a solution of 4-methyl-5-[(2-aminoethyl)thiomethyl]imidazole dihydrochloride (14.6 g.) in water (120 ml.). The solution was stirred at room temperature for 15 minutes and methyl isothiocyanate (5.15 g.) was added. After heating under reflux for 30 minutes, the solution was slowly cooled to 5. The product (13.1 g.) was collected and recrystallized from water to give N-methyl-N'-[2-((4-methyl-5-imidazolyl)methylthio)ethyl]thiourea, m.p. 150-152.
  • 6
  • [ 38603-72-4 ]
  • [ 556-61-6 ]
  • N-methyl-N'-[2-((5-methyl-4-imidazolyl)methylthio)ethyl]thiourea [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In water; Potassium carbonate (7.75 g) was added to a solution of 4-methyl-5-[(2-aminoethyl)thiomethyl]imidazole dihydrochloride (14.6 g) in water (120 ml). The solution was stored at room temperature for 15 minutes and methyl isothiocyanate (5.15 g) was added. After heating under reflux for 30 minutes, the solution was slowly cooled to 5. The product was collected and recrystallized from water to give N-methyl-N'-[2-((5-methyl-4-imidazolyl)methylthio)ethyl]thiourea, m.p.150-152.
With potassium carbonate; In water; Potassium carbonate (7.75 g.) was added to a solution of 4-methyl-5-[(2-aminoethyl)thiomethyl]imidazole dihydrochloride (14.6 g.) in water (120 ml.). The solution was stored at room temperature for 15 minutes and methyl isothiocyanate (5.15 g.) was added. After heating under reflux for 30 minutes, the solution was slowly cooled to 5 C. The product was collected and recrystallized from water to give N-methyl-N'-[2-((5-methyl-4-imidazolyl)-methylthio)ethyl]thiourea, m.p. 150-152 C.
With potassium carbonate; In water; (ii) Potassium carbonate (7.75 g.) was added to a solution of 4-methyl-5-[(2-aminoethyl)thiomethyl]imidazole dihydro-chloride (14.6 g.) in water (120 ml.). The solution was stored at room temperature for 15 minutes and methyl isothiocyanate (5.15 g.) was added. After heating under reflux for 30 minutes, the solution was slowly cooled to 5. The product (13.1 g.) was collected and recrystallized from water to give N-methyl-N'-[2-((5-methyl-4-imidazolyl)methylthio)ethyl]thiourea, m.p. 150-152. (Found: C, 44.5; H, 6.7; N, 23.0; S, 26.2. C9 H16 N4 S2 requires: C, 44.2; H, 6.6; N, 22.9; S, 26.2).
  • 7
  • [ 38603-72-4 ]
  • [ 556-61-6 ]
  • [ 34839-70-8 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In water; ii. Potassium carbonate (7.75 g.) was added to a solution of 4-methyl-5-[(2-aminoethyl)thiomethyl]imidazole dihydrochloride (14.6 g.) in water (120 ml.). The solution was stirred at room temperature for 15 minutes and methyl isothiocyanate (5.15 g.) was added. After heating under reflux for 30 minutes, the solution was slowly cooled to 5. The product (13.1 g) was collected and re-crystallized from water to give N-methyl-N'-[2-((5-methyl-4-imidazolyl) methylthio)ethyl]thiourea, m.p. 150-152.
  • 8
  • antihistamine [ No CAS ]
  • [ 156-57-0 ]
  • [ 38585-62-5 ]
  • [ 38603-72-4 ]
YieldReaction ConditionsOperation in experiment
In acetic acid; i. (a) A solution of 4-hydroxymethyl-5-methylimidazole hydrochloride (30.0 g) and cysteamine hydrochloride (23.0 g.) in acetic acid (200 ml.) was heated under reflux for 10 hours. Following cooling to 15-20, the solid which crystallized was collected and washed with isopropyl alcohol to give 4-methyl-5-[(2-aminoethyl)thiomethyl]-imidazole dihydrochloride (45.5 g), m.p. 189-192.
  • 9
  • [ 156-57-0 ]
  • [ 38585-62-5 ]
  • [ 38603-72-4 ]
YieldReaction ConditionsOperation in experiment
In acetic acid; i. a. A solution of 4-hydroxymethyl-5-methylimidazole hydrochloride (30.0g) and cysteamine hydrochloride (23.0g.) in acetic acid (200 ml.) was heated under reflux for 10 hours. Following cooling to 15-20, the solid which crystallized was collected and washed with isopropyl alcohol to give 4-methyl-5-[(2-aminoethyl)thiomethyl]-imidazole dihydrochloride (45.5g), m.p. 189-192.
In acetic acid; EXAMPLE 6 A solution of 4-hydroxymethyl-5-methylimidazole hydrochloride (30.0 g) and cysteamine hydrochloride (23.0 g) in acetic acid (200 ml) was heated under reflux for 10 hours. Following cooling to 15-20, the solid which crystallized was collected and washed with isopropyl alcohol to give 4-methyl-5-[(2-aminoethyl)thiomethyl]imidazole dihydrochloride m.p. 189-192.
In acetic acid; EXAMPLE 12 A solution of 4-hydroxymethyl-5-methylimidazole hydrochloride (30.0 g.) and cysteamine hydrochloride (23.0 g.) in acetic acid (200 ml.) was heated under reflux for 10 hours. Following cooling to 15-20 C., the solid which crystallized was collected and washed with isopropyl alcohol to give 4-methyl-5-[(2-aminoethyl)thiomethyl]-imidazole dihydrochloride, m.p. 189-192 C.
In concentrated aqueous hydrochloric acid; b. A solution of 4-hydroxymethyl-5-methylimidazole hydrochloride (30.0 g.) and cysteamine hydrochloride (23.0 g.) in concentrated aqueous hydrochloric acid (450 ml.) was heated under reflux for 17 hours. Concentration followed by re-evaporation with water afforded a residue which was dissolved in isopropyl alcohol, concentrated to low bulk and cooled to afford 4-methyl-5-[(2-aminoethyl)thiomethyl]imidazole dihydrochloride (40.6 g.), m.p. 185-191.
In acetic acid; i. a. A solution of 4-hydroxymethyl-5-methylimidazole hydrochloride (30.0 g.) and cysteamine hydrochloride (23.0 g.) in acetic acid (200 ml.) was heated under reflux for 10 hours. Following cooling to 15-20, the solid which crystallized was collected and washed with isopropyl alcohol to give 4-methyl-5-[(2-aminoethyl)thiomethyl]imidazole dihydrochloride (45.5 g), m.p. 189-192.
In concentrated aqueous hydrochloric acid; b. A solution of 4-hydroxymethyl-5-methylimidazole hydrochloride (30.0 g.) and cysteamine hydrochloride (23.0 g.) in concentrated aqueous hydrochloric acid (450 ml.) was heated under reflux for 17 hours. Concentration followed by re-evaporation with water afforded a residue which was dissolved in isopropyl alcohol, concentrated to low bulk and cooled to afford 4-methyl-5-[(2-aminoethyl)thiomethyl]-imidazole dihydrochloride (40.6 g.)m m.p. 185-191.
In acetic acid; (i) a. A solution of 4-hydroxymethyl-5-methylimidazole hydrochloride (30.0 g.) and cysteamine hydrochloride (23.0 g.) in acetic acid (200 ml.) ws heated under reflux for 10 hours. Following cooling to 15-20, the solid which crystallized was collected and washed with isopropyl alcohol to give 4-methyl-5-[(2-aminoethyl)thiomethyl]imidazole dihydrochloride (45.5 g.), m.p. 189-192.

  • 10
  • [ 156-57-0 ]
  • [ 38585-62-5 ]
  • N-methyl-N'-[2-((5-methyl-4-imidazolyl)methylthio)ethyl]thiourea [ No CAS ]
  • [ 38603-72-4 ]
YieldReaction ConditionsOperation in experiment
In concentrated aqueous hydrochloric acid; b. A solution of 4-hydroxymethyl-5-methylimidazole hydrochloride (30.0 g.) and cysteamine hydrochloride (23.0 g) in concentrated aqueous hydrochloric acid (450 ml.) was heated under reflux for 17 hours. Concentration followed by re-evaporation with water afforded a residue which was dissolved in isopropyl alcohol, concentrated to low bulk and cooled to afford 4-methyl-5-[(2-aminoethyl)thiomethyl]-imidazole dihydrochloride (40.6 g.), m.p. 185-191.
b. A solution of 4-hydroxymethyl-5-methylimidazole hydrochloride (30.0 g.) and cysteamine hydrochloride (23.0 g) in concentrated aqueous hydrochoric acid (450 ml.) was heated under reflux for 17 hours. Concentration followed by re-evaporation with water afforded a residue which was dissolved in isopropyl alcohol, concentrated to low bulk and cooled to afford 4-methyl-5-[(2-aminoethyl)thiomethyl]imidazole dihydrochloride (40.6 g.), m.p. 185-191.
  • 11
  • [ 822-36-6 ]
  • [ 156-57-0 ]
  • [ 38603-72-4 ]
YieldReaction ConditionsOperation in experiment
With paraformaldehyde; In hydrogenchloride; ethanol; EXAMPLE 1 42.0 Parts of 97.5% pure 4-methylimidazole, 56.8 parts of cysteamine hydrochloride and 18.0 parts of paraformaldehyde are dissolved in 207 parts of 37% strength aqueous hydrochloric acid, whilst cooling so that the temperature does not exceed 30 C. The mixture is heated in a closed glass-lined kettle for 5 hours at 110-120 C. and for a further 10 hours at 120 C. The hydrochloric acid is then distilled off under reduced pressure from a water-pump, at not more than 80 C., until the residue has almost been reduced to dryness, after which the latter is dissolved in 237 parts of boiling ethanol. The solution is cooled to 20 C. and the precipitate which forms is filtered off and dried. 81.9 Parts (constituting the 1st fraction) of 4-methyl-5-[(2-aminoethyl)-thiomethyl]-imidazole dihydrochloride, of melting point 179-180 C., are obtained. The filtrate is evaporated to about half its volume and is cooled to 20 C., and the precipitate is filtered off. After drying, a further 12.7 parts (constituting the 2nd fraction) of melting point 149-154 C. are obtained. Fractions 1 and 2 are combined and recrystallized from 315 parts of glacial acetic acid. After drying at 10 mm Hg and 90 C., 82.4 parts (67.5%) of 4-methyl-5-[(2-aminoethyl)-thiomethyl]-imidazole dihydrochloride of melting point 190-191 C. are obtained.
  • 12
  • [ 156-57-0 ]
  • [ 51605-33-5 ]
  • [ 38603-72-4 ]
YieldReaction ConditionsOperation in experiment
(b) 84 parts of 4-methyl-5-chloromethyl-imidazole hydrochloride, in the form of a fine powder, and 57 parts of cysteamine hydrochloride, also in the form of a fine powder, are mixed intimately and the mixture is heated in a solidstate reactor for 2 hours at 80 and then for 7 hours at 100; the progress of the reaction can be followed by NMR spectroscopy or from the evolution of hydrogen chloride. 120 parts (98%) of 4-methyl-5-[(2-amino-ethyl)-thiomethyl]-imidazole dihydrochloride are obtained; the substance melts at 186-189 C., after first sintering at about 181 C. A single recrystallization of the product from ethanol raises the melting point to 193-195 C.
  • 13
  • N,N-dimethyl-[[[2-[(1-methylthio-2-nitroethenyl)amino]ethyl]thio]methyl]-2-furanmethanamine [ No CAS ]
  • [ 38603-72-4 ]
  • N-[2-[[5-[(Dimethylamino)methyl]-2-furanylmethyl]thio]ethyl]-N'-[2-[(4-methyl-1H-imidazol-5-ylmethyl)thio]ethyl]-2-nitro-1,1-ethene diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium hydroxide; In methanol; EXAMPLE 2 N-[2-[[5-[(Dimethylamino)methyl]-2-furanylmethyl]thio]ethyl]-N'-[2-[(4-methyl-1H-imidazol-5-ylmethyl)thio]ethyl]-2-nitro-1,1-ethene diamine A mixture of potassium hydroxide (0.184 g), 4-methyl-5-[(2-aminoethyl)thiomethyl]imidazole dihydrochloride (0.4 g) and N,N-dimethyl[[[2-[(1-methylthio-2-nitroethenyl)amino]ethyl]thio]methyl]-2-furanmethanamine (1.14 g) in methanol (5 ml) was evaporated to dryness in vacuo and the residue heated at 98-100 C. for 8 hours. The semi-solid was extracted with hot acetonitrile (3*10 ml) and the combined extracts were evaporated to dryness to give an oil which was subjected to column chromatography (silica/methanol-0.88 ammonia 79:1). The appropriate elude was evaporated to dryness to give the title compound as a hemihydrate as a semi-solid (0.43 g). Found: C,49.6; H,6.9; N,17.8%. C19 H30 N6 O3 S2.1/2H2 O requires: C,49.2; H,6.7; N,18.1%.
  • 14
  • [ 38603-72-4 ]
  • [ 76181-71-0 ]
  • 15
  • [ 38603-72-4 ]
  • N-methyl-N'-[2-((4-methyl-5-imidazolyl)methylthio)ethyl]guanidine dihydrochloride [ No CAS ]
 

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