[ CAS No. 60-56-0 ] {[proInfo.proName]}

Name: 60-56-0|1-Methyl-1H-imidazole-2(3H)-thione|99%
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Quality Control of [ 60-56-0 ]

COA NMR CNMR HPLC LC-MS

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Product Details of [ 60-56-0 ]

CAS No. :	60-56-0	MDL No. :	MFCD00179321
Formula :	C₄H₆N₂S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	PMRYVIKBURPHAH-UHFFFAOYSA-N
M.W :	114.17	Pubchem ID :	1349907
Synonyms :	Thiamazole;NSC 38608;Northyx;Favistan	Chemical Name :	1-Methyl-1H-imidazole-2(3H)-thione

Calculated chemistry of [ 60-56-0 ]

Physicochemical Properties

Num. heavy atoms :	7
Num. arom. heavy atoms :	5
Fraction Csp3 :	0.25
Num. rotatable bonds :	0
Num. H-bond acceptors :	0.0
Num. H-bond donors :	1.0
Molar Refractivity :	30.88
TPSA :	52.81 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.24 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.48
Log Po/w (XLOGP3) :	-0.34
Log Po/w (WLOGP) :	1.08
Log Po/w (MLOGP) :	-0.56
Log Po/w (SILICOS-IT) :	2.06
Consensus Log Po/w :	0.74

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-0.86
Solubility :	15.7 mg/ml ; 0.137 mol/l
Class :	Very soluble
Log S (Ali) :	-0.31
Solubility :	56.3 mg/ml ; 0.493 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.85
Solubility :	16.1 mg/ml ; 0.141 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.32

Safety of [ 60-56-0 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P201-P202-P261-P272-P280-P302+P352+P333+P313+P363-P308+P313-P405-P501	UN#:	N/A
Hazard Statements:	H303-H317-H361	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 60-56-0 ]

* 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 [ 60-56-0 ]
Downstream synthetic route of [ 60-56-0 ]

[ 60-56-0 ] Synthesis Path-Upstream 1~13

1
[ 186581-53-3 ]
[ 60-56-0 ]
[ 14486-52-3 ]

Reference： [1] Patent: US5663164, 1997, A,

2
[ 60-56-0 ]
[ 77-78-1 ]
[ 14486-52-3 ]

Reference： [1] Magnetic Resonance in Chemistry, 1985, vol. 23, # 3, p. 166 - 169

3
[ 60-56-0 ]
[ 74-88-4 ]
[ 14486-52-3 ]

Reference： [1] Journal of Heterocyclic Chemistry, 1995, vol. 32, # 1, p. 227 - 234
[2] Journal of Heterocyclic Chemistry, 1995, vol. 32, # 1, p. 227 - 234

4
[ 60-56-0 ]
[ 541-41-3 ]
[ 22232-54-8 ]

Reference： [1] Journal of the Chemical Society, 1956, p. 1103,1106
[2] Patent: US2671088, 1952, ,
[3] Patent: US2815349, 1956, ,

5
[ 110-86-1 ]
[ 60-56-0 ]
[ 541-41-3 ]
[ 22232-54-8 ]

Reference： [1] Journal of the Chemical Society, 1956, p. 1103,1106
[2] Patent: US2671088, 1952, ,
[3] Patent: US2815349, 1956, ,

6
[ 60-56-0 ]
[ 16681-59-7 ]

Reference： [1] Dalton Transactions, 2011, vol. 40, # 43, p. 11382 - 11384

7
[ 616-47-7 ]
[ 60-56-0 ]

Yield	Reaction Conditions	Operation in experiment
82.54%	Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -10℃; for 1.5 h; Stage #2: With sulfur In tetrahydrofuran; hexane for 9 h; Reflux	N-methylimidazole 8.21 g (100 mmol) and 80 ml of tetrahydrofuran were added to a three-necked reaction flask and then cooled to -5 ° C. A solution of n-butyllithium-n-hexane (50 ml, n-butyllithium, MOL / L). After the dropwise addition, the reaction was incubated at -5 ° C for 1 hour. Then, 4.16 g (130 mmol) of elemental sulfur was added portionwise at the same temperature, and the temperature was raised for 8 hours. Thin layer chromatography was used to detect the raw material spots, and then quenched in an ice-water bath. The pH was adjusted to 6.0 to 6.5 by the addition of dilute hydrochloric acid, and then the reaction system was concentrated to dryness under pressure. The concentrated solid was dissolved in ethyl acetate and activated carbon. The reaction mixture was decolorized by refluxing for about 1 hour. The filtrate was concentrated under reduced pressure to give 9.41 g of methimazole as a pale yellow solid. The yield was 82.54percent and the purity was 100percent (gas chromatography).

Reference： [1] Patent: CN105541724, 2016, A, . Location in patent: Paragraph 0029; 0031; 0032

8
[ 333-20-0 ]
[ 20677-73-0 ]
[ 60-56-0 ]

Yield	Reaction Conditions	Operation in experiment
150 kg	With hydrogenchloride In water at 20 - 30℃; Large scale	in 5 of adding the reactor 410 kg methylamino acetaldehyde diethyl acetal, 270 kg of potassium thiocyanate and 500 kg of purified water, stirring the mixture at room temperature after completely dissolved, to the 5 of the pre-prepared reaction in the cauldron adds by drops 1mol/L dilute hydrochloric acid 1000 kg, control of the temperature of the reaction solution in the 30 °C left and right.After the reaction, the reaction liquid water is removed by reduced pressure distillation, the resulting solid with ethyl acetate is dissolved again, after the undissolved substances, ethyl acetate is removed by reduced pressure distillation. The resulting solid is dissolved in purified water, adjust the pH to 1, the cooling crystallization to obtain the purity is greater than 99percent of the product, vacuum drying to obtain 2-mercapto-1-methyl imidazole final product 150 kg, yield of 47.2percent.

Reference： [1] Patent: CN103214421, 2016, B, . Location in patent: Paragraph 0024; 0025

9
[ 540-72-7 ]
[ 122-07-6 ]
[ 60-56-0 ]

Yield	Reaction Conditions	Operation in experiment
0.86 kg	With hydrogenchloride In water at 20 - 60℃;	1.44kg sodium thiocyanate and 8.9kg of purified water into the loop reactor,Dissolved under stirring at room temperature, added 1.60kg methanolactam methanol,Under stirring, 1.44 kg of hydrochloric acid (concentration 36percent -40percent) was added dropwise at room temperature and the temperature was controlled below 30 ° C.,About one hour was added dropwise, ph value of 1-2, at 50-60 for 13 hours, cooled to room temperature for 8 hours.The water was distilled off under reduced pressure, 5 L of ethyl acetate and 500 g of anhydrous sodium sulfate were added, and the mixture was refluxed for 30 minutes and filtered with hot water.The filtrate was heated to distillation, about the remaining one-third of the ethyl acetate, cooled to 0 ° C, 0-5 ° C for 2-3 hours, filtered, washed with cold ethyl acetate and dried in vacuo to giveMethimazole 0.86kg,The yield was 59.3percent. GC determination, product purity 99.5percent

Reference： [1] Patent: CN107353253, 2017, A, . Location in patent: Paragraph 0033; 0034

10
[ 63348-55-0 ]
[ 23269-08-1 ]
[ 60-56-0 ]

Reference： [1] Heterocycles, 1982, vol. 17, p. 125 - 138

11
[ 3129-90-6 ]
[ 20677-73-0 ]
[ 60-56-0 ]

Reference： [1] European Journal of Inorganic Chemistry, 2003, # 13, p. 2502 - 2511

12
[ 7647-01-0 ]
[ 333-20-0 ]
[ 20677-73-0 ]
[ 60-56-0 ]

Reference： [1] Journal of the American Chemical Society, 1949, vol. 71, p. 4000

13
[ 60-56-0 ]
[ 55694-81-0 ]

Reference： [1] Tetrahedron Asymmetry, 1997, vol. 8, # 21, p. 3559 - 3562
[2] Patent: US2009/215775, 2009, A1,
[3] Patent: WO2004/31139, 2004, A1, . Location in patent: Page 19
[4] Journal of Medicinal Chemistry, 2012, vol. 55, # 15, p. 6738 - 6750

[ 60-56-0 ] Synthesis Path-Downstream 1~88

1
[ 110-86-1 ]
[ 60-56-0 ]
[ 541-41-3 ]
[ 22232-54-8 ]

Reference： [1]Journal of the Chemical Society,1956,p. 1103,1106

2
[ 60-56-0 ]
[ 541-41-3 ]
[ 22232-54-8 ]

Reference： [1]Journal of the Chemical Society,1956,p. 1103,1106

3
[ 60-56-0 ]
[ 77-78-1 ]
[ 14486-52-3 ]

Reference： [1]Magnetic Resonance in Chemistry,1985,vol. 23,p. 166 - 169

4
[ 63810-78-6 ]
[ 60-56-0 ]
[ 96591-98-9 ]

Reference： [1]European Journal of Medicinal Chemistry,1984,vol. 19,p. 559 - 565

5
[ 40741-46-6 ]
[ 60-56-0 ]
[ 96591-89-8 ]

Reference： [1]European Journal of Medicinal Chemistry,1984,vol. 19,p. 559 - 565

6
[ 33263-43-3 ]
[ 60-56-0 ]
[ 96591-90-1 ]

Reference： [1]European Journal of Medicinal Chemistry,1984,vol. 19,p. 559 - 565

7
[ 3034-48-8 ]
[ 60-56-0 ]
[ 39259-57-9 ]

Reference： [1]European Journal of Medicinal Chemistry,1981,vol. 16,p. 233 - 239

8
[ 60-56-0 ]
[ 74-88-4 ]
[ 14486-52-3 ]

Reference： [1]Journal of Heterocyclic Chemistry,1995,vol. 32,p. 227 - 234
[2]Journal of Heterocyclic Chemistry,1995,vol. 32,p. 227 - 234

9
[ 6429-10-3 ]
[ 60-56-0 ]
2-[2-(1H-Imidazol-4-yl)-ethylsulfanyl]-1-methyl-1H-imidazole [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,1995,vol. 30,p. 881 - 889

10
[ 4897-25-0 ]
[ 60-56-0 ]
1-Methyl-5-(1-methyl-1H-imidazol-2-ylsulfanyl)-4-nitro-1H-imidazole [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 2690 - 2695

11
[ 60-56-0 ]
[ 55694-81-0 ]

Yield	Reaction Conditions	Operation in experiment
	In sulfuric acid;	2-chlorosulfonyl-1-methylimidazole Bleach (12% w/w aq, 110 ml) was cautiously added dropwise to a solution of 2-mercapto-1-methylimidazole (2.0 g) in conc. H2SO4 (50 ml) cooled to 0 C. After stirring 30 minutes at 0 C. the mixture was diluted with H2O (30 ml) and dichloromethane (30 ml). The aqueous layer was re-extracted with dichloromethane and the combined organic layers dried (MgSO4) and evaporated to give the product as an oil (730 mg).
	With sodium hypochlorite; sulfuric acid; In water; at 0℃; for 0.5h;	Bleach (12% w/w aq, 110 ml) was cautiously added dropwise to a solution of 2-mercapto-1-methylimidazole (2.0 g) in conc. [H2SO4] (50 ml) cooled to [0C.] After stirring 30 minutes at [0C] the mixture was diluted with [H20] (30 ml) and dichloromethane (30 ml). The aqueous layer was re-extracted with dichloromethane and the combined organic layers dried [(MGS04)] and evaporated to give the product as an oil (730 mg).

Reference： [1]Tetrahedron Asymmetry,1997,vol. 8,p. 3559 - 3562
[2]Patent: US2009/215775,2009,A1
[3]Patent: WO2004/31139,2004,A1 .Location in patent: Page 19
[4]Journal of Medicinal Chemistry,2012,vol. 55,p. 6738 - 6750
[5]Journal of Sulfur Chemistry,2020

12
[ 3347-62-4 ]
[ 60-56-0 ]
K⁽¹⁺⁾*[HB(C₃H₂N₂(S)CH₃)2(C₃HN₂(CH₃)C₆H₅)]^(1-)=K[HB(C₃H₂N₂(S)CH₃)2(C₃HN₂(CH₃)C₆H₅)] [ No CAS ]

Reference： [1]European Journal of Inorganic Chemistry,2003,p. 2502 - 2511

13
[ 4415-73-0 ]
[ 60-56-0 ]
[ 568591-46-8 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 5057 - 5068

14
[ 913286-78-9 ]
[ 60-56-0 ]
7-[(1-methyl-1H-imidazol-2-yl)thio]methyl}-2-(1,3-thiazol-2-yl)-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With tributylphosphine; 1,1'-azodicarbonyl-dipiperidine; In tetrahydrofuran; at 20℃; for 2h;	Example 255 7-[(1-Methyl-1H-imidazol-2-yl)thio]methyl}-2-(1,3-thiazol-2-yl)-1H-indole, A solution of [2-(1,3-thiazol-2-yl)-1H-indol-7-yl]methanol (0.095 g), 1-methyl-1H-imidazole-2-thiol (0.047 g) and tributylphosphine (0.251 g) in tetrahydrofuran (7 mL) was stirred, 1,1'-(azodicarbonyl)dipiperidine (0.312 g) was added, and the mixture was stirred at room temperature for 2 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=30:70 - 70:30) to give the title compound (0.089 g, yield 66%) as colorless crystals. MS m/z 327(M+H+).

Reference： [1]Patent: EP1873144,2008,A1 .Location in patent: Page/Page column 192

15
1-[2-(1,3-thiazol-2-yl)-1H-indol-7-yl]ethanol [ No CAS ]
[ 60-56-0 ]
7-{1-[(1-methyl-1H-imidazol-2-yl)thio]ethyl}-2-(1,3-thiazol-2-yl)-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With tributylphosphine; 1,1'-azodicarbonyl-dipiperidine; In tetrahydrofuran; at 20℃; for 1h;	Example 257 7-{1-[(1-Methyl-1H-imidazol-2-yl)thio]ethyl}-2-(1,3-thiazol-2-yl)-1H-indole A solution of 1-[2-(1,3-thiazol-2-yl)-1H-indol-7-yl]ethanol (0.089 g), 1-methyl-1H-imidazole-2-thiol (0.046 g) and tributylphosphine (0.458 g) in tetrahydrofuran (7 mL) was stirred, 1,1'-(azodicarbonyl)dipiperidine (0.584 g) was added, and the mixture was stirred at room temperature for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=30:70 - 70:30) to give the title compound (0.110 g, yield 89%) as colorless crystals. MS m/z 341 (M+H+).

Reference： [1]Patent: EP1873144,2008,A1 .Location in patent: Page/Page column 192-193

16
[ 74367-78-5 ]
[ 60-56-0 ]
C₁₁H₁₀N₄O₄S [ No CAS ]

Reference： [1]Zeitschrift fur Naturforschung, B: Chemical Sciences,2006,vol. 61,p. 101 - 107

17
[ 138286-76-7 ]
[ 60-56-0 ]
[ 212769-61-4 ]

Yield	Reaction Conditions	Operation in experiment
96%		Example 39 2-(1-methyl-1H-imidazol-2-ylsulfanyl)-octanoic acid hydroxyamide 2-(1-methyl-1H-imidazol-2-ylsulfanyl)-octanoic acid ethyl ester was prepared according to the general method as outlined in example 9.. Starting from <strong>[138286-76-7]ethyl 2-bromooctanoate</strong> (12.1 g, 48 mmol) and 1-methyl-2-mercapto imidazole (5 g, 43.8 mmol). Yield: 12 g (96%); clear oil; MS: 285 (M+H)+.
96%		EXAMPLE 39 2-(1-methyl-1H-imidazol-2-ylsulfanyl)-octanoic acid hydroxyamide 2-(1-methyl-1H-imidazol-2-ylsulfanyl)-octanoic acid ethyl ester was prepared according to the general method as outlined in example 9.. Starting from <strong>[138286-76-7]ethyl 2-bromooctanoate</strong> (12.1 g, 48 mmol) and 1-methyl-2-mercapto imidazole (5 g, 43.8 mmol). Yield: 12 g (96%); clear oil; MS: 285 (M+H)+.

Reference： [1]Patent: EP970046,2003,B1 .Location in patent: Page 31
[2]Patent: US6342508,2002,B1 .Location in patent: Page column 38

18
[ 33252-29-8 ]
[ 60-56-0 ]
2-Cyano-6-(1-methyl-1H-imidazol-2-yl)thiopyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium hydride; In DMF (N,N-dimethyl-formamide); at 70℃; for 18h;	Reference Example 98 2-Cyano-6-(1-methyl-1H-imidazol-2-yl)thiopyridine 2-Mercapto-1-methyl-1H-imidazole (0.91 g, 7.94 mmol) and sodium hydride (60 % in oil, 0.35 g, 8.66 mmol) were dissolved in DMF (30 ml), and <strong>[33252-29-8]2-chloro-6-cyanopyridine</strong> (1.05 g, 3.00 mmol) was added thereto.. The reaction mixture was stirred at 70 C for 18 hrs and combined with ethyl acetate and water.. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate.. The solvent was evaporated, and the residue was recrystallized from n-hexane-ethyl acetate to give the titled compound (1.71 g, ca. 100 %) as pale yellow crystals.1H-NMR (CDCl3) delta: 3.79 (3H, s), 7.21-7.23 (1H, m), 7.63-7.66 (1H, m), 8.85 (1H, t, J = 4.8 Hz), 8.25 (1H, d, J = 7.6 Hz), 8.56 (1H, d, J = 4.8 Hz). IR(KBr): 2231, 1570, 1550, 1433, 1373, 1167, 1152, 1086, 983, 798 cm-1.

Reference： [1]Patent: EP1424336,2004,A1 .Location in patent: Page 201

19
[ 78056-39-0 ]
[ 60-56-0 ]
[ 849236-50-6 ]

Yield	Reaction Conditions	Operation in experiment
98%	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 60℃; for 5h;	Step 1: 5- (L-METHYL-LH-IMIDAZOL-2-YLTHIO)-4-FLUORO-2-NITROBENZENAMINE (208a): [0363] To a stirred solution of 206 (500mg, 2.8 MMOL) in DMF (20 mL), was added 1-METHYL-LH- IMIDAZOLE-2-THIOL (207a, 2.8 MMOL, 328 mg) and potassium carbonate (1.58 g, 11.49 MMOL). The reaction mixture was stirred at 60 FOR 5 hours. Ethyl acetate was added and K2CO3 was removed by filtration. The filtrate was concentrated, evaporated under reduced pressure and the residue was purified by flash chromatography on silica gel, eluents hexane-EtOAc (1: 2), then EtOAc (100%) to afford 208a (751MG, 98% yield). MS: (CALC.) 268.3 ; (obt. ) 269.1 (MH) +.

Reference： [1]Patent: WO2005/30704,2005,A1 .Location in patent: Page/Page column 212

20
[ 889686-58-2 ]
[ 60-56-0 ]
[ 889687-25-6 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 125℃; for 15h;	Step 1: 2- {r6-(4-Fluorophenyl)-2-naphthyl1thio}-l -methyl- lH-imidazole; A mixture of 6-(4-fluorophenyl)-2-naphthyl trifluoromethanesulfonate (Ex 1 Step 2, 150 mg, 0.41 mmol), 1 -methyl- lH-imidazole-2-thiol (47 mg, 0.41 mmol), tris(dibenzylideneacetone)dipalladium(0) (16 mg), 4,5- bis(diphenylphosphino)-9,9-dimethylxanthene (20 mg) and diisopropylethylamine (0.15 mL, 0.82 mmol) in dioxane (3 mL) was heated to 125C under nitrogen for 15 h. The cooled reaction mixture was poured into water and extracted with ethyl acetate (x3). The combined organic layers were washed with water and EPO <DP n="37"/>brine, dried (MgSO4) and evaporated in vacuo. The residue was purified by flash column chromatography on silica, eluting with 25% ethyl acetate/isohexane, to give the title compound as an oil (125 mg). 1H NMR (500 MHz, CDCl3): delta 7.90 (1 H, s), 7.75 (2 H, t, J = 8.6 Hz), 7.66-7.59 (4 H, m), 7.27 (2 H, m), 7.15 (2 H, m), 7.10 (1 H, s), 3.65 (3 H, s); m/z (ES+) 335 [MH+].

Reference： [1]Patent: WO2006/59149,2006,A1 .Location in patent: Page/Page column 35-36

21
[ 108-48-5 ]
[ 147539-05-7 ]
[ 60-56-0 ]
[ 147520-12-5 ]

Yield	Reaction Conditions	Operation in experiment
64%	With hydrogenchloride; sodium hydrogencarbonate; In ethanol; water; acetone;	EXAMPLE 4 1-methyl-2-[3-[(p-isobutyloxycarbonyl)-phenoxy]-2-hydroxy-propylthio]-imidazole hydrochloride The suspension of 5.73 g (50 mmoles) of 1-methyl-2-mercapto-imidazole in absolute ethanol (100 ml) is added with 2,6-lutidine in catalytic amount and there is dropwise added the solution of isobutyl p-(2,3-epoxy)-propyloxybenzoate (12.5 g; 50 mmoles) in absolute ethanol (50 mmoles) at room temperature under stirring. The mixture is heated to reflux for 6 hours. The solvent is evaporated under vacuum, the residue is taken with ethyl acetate and washed with aqueous saturated solution of sodium bicarbonate and with water. The mixture is made anhydrous over anhydrous sodium sulfate and concentrated to an oil. The lutidine is completely removed by evaporation under vacuum. The product, dissolved in acetone, is treated with an excess of 37% aqueous hydrochloric acid and maintained under stirring until the salification is completed. The mixture is concentrated to dryness under vacuum with subsequent additions of toluene/ethanol, the solid is comminuted with ethyl ether/hexane and is crystallized from a mixture of acetone/ethyl acetate. The product is obtained with a yield of 64% and has melting point 104-108 C. By repeating the operating method of example 4 the following derivatives are prepared:
64%	With hydrogenchloride; sodium hydrogencarbonate; In ethanol; water; ethyl acetate; acetone;	EXAMPLE 4 1-methyl-2-[3-[(p-isobutyloxycarbonyl)-phenoxy]-2-hydroxy-propylthio]-imidazole hydrochloride The suspension of 5.73 g (50 mmoles) of 1-methyl-2-mercapto-imidazole in absolute ethanol (100 ml) is added with 2,6-lutidine in catalytic amount and there is dropwise added the solution of isobutyl p-(2,3-epoxy)-propyloxybenzoate (12.5 g; 50 mmoles) in absolute ethanol (50 mmoles) at room temperature under stirring.The mixture is heated to reflux for 6 hours. The solvent is evaporated under vacuum, the residue is taken with ethyl acetate and washed with aqueous saturated solution of sodium bicarbonate and with water. The mixture is made anhydrous over anhydrous sodium sulfate and concentrated to an oil. The lutidine is completely removed by evaporation under vacuum. The product, dissolved in acetone, is treated with an excess of 37% aqueous hydrochloric acid and maintained under stirring until the salification is completed.The mixture is concentrated to dryness under vacuum with subsequent additions of toluene/ethanol, the solid is comminuted with ethyl ether/hexane and is crystallized from a mixture of acetone/ethyl acetate.The product is obtained with a yield of 64% and has melting point 104-108oC.. By repeating the operating method of example 4 the following derivatives are prepared:

Reference： [1]Patent: US5470858,1995,A
[2]Patent: EP520552,1992,A1

22
[ 3056-18-6 ]
methanolic ammonia [ No CAS ]
[ 162684-69-7 ]
[ 79069-13-9 ]
[ 60-56-0 ]
[ 162684-32-4 ]

Yield	Reaction Conditions	Operation in experiment
43%		EXAMPLE 2 2-Chloro-N-[(R)-1-(1-methyl-2-imidazolyl)thio-2-propyl]adenosine The title compound was prepared according to method A as described above in Example 1 by reacting (R)-1-(1-methyl-2-imidazolyl)thio-2-propylamine hydrochloride [prepared using the same method as described in Example 1 from 2-mercapto-1-methylimidazole (3.31 g, 29 mmol) and 2-[(R)-N-tert-butyloxycarbonyl]amino-1-propanol (5.08 g, 29 mmol) followed by acidic hydrolysis] (2.30 g, 11.1 mmol) with 9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-2,6-dichloro-9H-purine (2.46 g, 5.5 mmol), followed by debenzoylation of the purified product using methanolic ammonia. This provided the title 2-chloro-N[(R)-1-(1-methyl-2-imidazolyl)-thio-2-propyl]adenosine (1.1 g, 43%) as a foam after column chromatography. 1 H NMR (DMSO-d6) delta 1.28 (3H, d, --CHCH3), 3.53-3.60 (1 H, m, H-5'a), 3.63-3.70 (1H, m, H-5'b), 3.95 (1H, q, H- 4'), 4.13 (1H, q, H-3'), 4.51 (1 H, q, H-2'), 5.07 (1H, t, 5'-OH), 5.22, 5.50 (2H, 2d, 2'- and 3'-OH), 5.82 (1H, d, H-1'), 6.92 (1H, s, Ar-H) 7.20 (1H, s, Ar-H), 8.40 (1H, s, H-8), 8.55 (1H, s, N--H). HPLC retention time 19.3 min [gradient elution, 20-80% acetonitrile/water (containing 0.1% TFA)].

Reference： [1]Patent: US5484774,1996,A

23
[ 186581-53-3 ]
[ 60-56-0 ]
[ 14486-52-3 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane;	STEP A 2-methylthio-1-methyl-imidazole 10 ml of a solution of 1.5% diazomethane in methylene chloride were added in 3 portions over 15 minutes at 0 C. to a solution of 1.14 g of 2-mercapto-1-methyl-imidazole in 5 ml of methylene chloride and after stirring at 0 C. for one hour, a second addition of 10 ml of the diazomethane in methylene chloride solution was made. The mixture was stirred at 20 C. for one hour and was then evaporated to dryness under reduced pressure. The residue was chromatographed over silica and was eluted with a 1-1 methylene chloride-ethyl acetate mixture to obtain 1 g of 2-methylthio-1-methyl-imidazole.

Reference： [1]Patent: US5663164,1997,A

24
[ 174524-26-6 ]
[ 60-56-0 ]
[ 174524-07-3 ]

Yield	Reaction Conditions	Operation in experiment
71%	With potassium carbonate; In N,N-dimethyl-formamide;	EXAMPLE 4 A mixture of 3-acetyl-2-bromomethyl-4-(3,4-dimethoxyphenyl)-6,7-dimethoxyquinoline (1.5 g), 1-methyl-2-mercaptoimidazole (0.417 g), potassium carbonate (0.495 g) and N,N-dimethylformamide (20 ml) was stirred at room temperature for 3 hours. The reaction mixture was poured into water, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, and dried over magnesium sulfate. Evaporation of the solvent gave 3-acetyl-4-(3,4-dimethoxy-phenyl)-6,7-dimethoxy-2-[(1-methylimidazol-2-yl)thiomethyl]-quinoline (1.1 g, 71%). This compound was recrystallized from ethanol to give colorless prisms, mp. 175-176 C.

Reference： [1]Patent: US5641788,1997,A

25
[ 5122-82-7 ]
[ 60-56-0 ]
[ 749843-47-8 ]

Yield	Reaction Conditions	Operation in experiment
79%	With triethylamine; In acetonitrile; at 20℃; for 20h;	l-Adamantan-l-yl-2-(l-methyl-lH-imidazol-2-yIsulfanyI)-ethanone (STX1898, XDS04042); To a solution of adamantan-1-yl bromomethyl ketone (256 mg, 1.0 mmol) in acetonitrile (5 mL) was added 2-mecapto 1-methylimidazole (114 mg, 1.0 mmol), followed by triethylamine (0.5 mL). The mixture was stirred at ambient temperature for 20 h, partitioned between ethyl acetate and brine. The organic phase was washed with brine, dried over sodium sulphate and concentrated in vacuo to give the crude product. Purification with flash column (hexane-ethyl acetate; gradient elution) yielded the title compound as off-white solid (230 mg, 79%). mp 65-69 C; TLC single spot at Rf. 0.51 (50% EtOAc/hexane); 1H NMR (270 MHz, CDCl3) delta 1.63-1.81 (6H, m, 3 x CH2), 1.82 (6H, d, J= 2.3 Hz, 3 x CH2), 2.03 (3H, broad, 3 x CH), 3.64 (3H, s, CH3), 4,23 (2H, s, CH2), 6.89 (IH, d, J= 1.2 Hz, ArH) and 7.01 (IH,

Reference： [1]ChemMedChem,2011,vol. 6,p. 1439 - 1451
[2]Patent: WO2006/100502,2006,A1 .Location in patent: Page/Page column 127

26
[ 1317-39-1 ]
[ 95-51-2 ]
[ 60-56-0 ]
[ 7440-66-6 ]
2-((2-chlorophenyl)thio)-1H-imidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.1 g (63%)	With ammonium hydroxide; sodium nitrite; In sulfuric acid; water;	Method B. A mixture of 0.6 g of zinc powder was stirred for 20 minutes at 60 C. with 25 ml of 1N sulfuric acid and then filtered. To the filtrate was added 0.35 g of cuprous oxide followed by 0.9 g (7.8 mmoles) of 2-mercapto-1-methylimidazole. 2-Chloroaniline (1 g, 7.8 mmoles) in 36 ml of 1N sulfuric acid was diazotized by cooling in an icebath followed by the dropwise addition of a solution of 0.57 g (8.2 mmoles) of sodium nitrite in 5 ml of water. The diazonium solution was then added over 30 minutes, and at 0 C. to the above solution of 2-mercapto-1-methylimidazole. The mixture was stirred at 0 for 2 hours and then at room temperature for 2 hours. The mixture was decanted and made basic by treatment with ammonium hydroxide and extracted with ether. The organics were washed with saturated sodium chloride solution, dried and concentrated. The residue was dissolved in a small amount of dichloromethane and filtered through silica gel using ether as the eluent. The fractions containing the product were combined and concentrated to give 1.1 g (63%) of the product, identical to the product obtained in Method A.

Reference： [1]Patent: US4973599,1990,A

27
[ 81-07-2 ]
[ 60-56-0 ]
[ 100-11-8 ]
[ 50968-73-5 ]

Yield	Reaction Conditions	Operation in experiment
89%	With 1,1,1,3,3,3-hexamethyl-disilazane; In N,N,N,N,N,N-hexamethylphosphoric triamide; water; toluene; Petroleum ether;	EXAMPLE 28 A mixture consisting of 2.85 g (25 mmoles) of 1-methyl-2-mercaptoimidazole, 22 mg (0.12 mmoles) of saccharin, 20 ml of toluene and 5.2 ml (25 mmoles) of hexamethyldisilazane was refluxed for 1 hour and after cooling to room temperature, 5.40 g (25 mmoles) of 4-nitrobenzyl bromide and then 5 ml of hexamethylphosphoric triamide were added to the mixture which contained 1-methyl-2-(trimethylsilylthio)-imidazole. After stirring for 2 hours at room temperature, the mixture was diluted to 150 ml with ethyl acetate and the solution thus obtained was washed three times with 50 ml of a saturated sodium bicarbonate solution and then twice with 20 ml of water. The organic layer was dried, filtered and evaporated to dryness and the crystalline residue was washed with 100 ml of petroleum ether (boiling range 60-80 C.) and then vacuum dried to obtain 5.54 g (89% yield) of 1-methyl-2-(4-nitrobenzylthio)-imidazole melting to 74-77 C. Crystallization of a sample from ethanol raised the melting point to 77.5-78.0 C.

Reference： [1]Patent: US4496720,1985,A

28
[ 212769-61-4 ]
[ 138286-76-7 ]
[ 60-56-0 ]
2-(1-methyl-1H-imidazol-2-ylsulfanyl)-octanoic acid hydroxyamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 39 2-(1-methyl-1H-imidazol-2-ylsulfanyl)-octanoic acid hydroxyamide 2-(1-methyl-1H-imidazol-2-ylsulfanyl)-octanoic acid ethyl ester was prepared according to the general method as outlined in example 9. Starting from <strong>[138286-76-7]ethyl 2-bromooctanoate</strong> (12.1 g, 48 mmol) and 1-methyl-2-mercapto imidazole (5 g, 43.8 mmol). Yield: 12 g (96%); clear oil; MS: 285 (M+H)+. Starting from 2-(1-methyl-1H-imidazol-2-ylsulfanyl)-octanoic acid ethyl ester (12 gm, 42.2 mmol) 10.2 g (Yield: 95%) of 2-(1-methyl-1H-imidazol-2-ylsulfanyl)-octanoic acid was isolated as colorless solid by following the procedure as outlined in example 9. MP: 95 C, MS: 257.1 (M+H)+. Starting from 2-(1-methyl-1H-imidazol-2-ylsulfanyl)-octanoic acid (7.84 g, 30.6 mmol) and following the procedure as outlined in example 1, 2.77 g of 2-(1-methyl-1H-imidazol-2-ylsulfanyl)-octanoic acid hydroxyamide was isolated as colorless solid. Yield: 33%, MP: 125 C; MS: 272.2 (M+H).

Reference： [1]Patent: US6172057,2001,B2

29
[ 212769-61-4 ]
[ 138286-76-7 ]
[ 60-56-0 ]
[ 212769-62-5 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 39 2-(1-methyl-1-imidazol-2-ylsulfanyl)-octanoic acid hydroxyamide 2-(1-methyl-1H-imidazol-2-ylsulfanyl)-octanoic acid ethyl ester was prepared according to the general method as outlined in example 9. Starting from <strong>[138286-76-7]ethyl 2-bromooctanoate</strong> (12.1 g, 48 mmol) and 1-methyl-2-mercapto imidazole (5 g, 43.8 mmol). Yield: 12 g (96%); clear oil; MS: 285 (M+H)+. Starting from 2-(1-methyl-1H-imidazol-2-ylsulfanyl)-octanoic acid ethyl ester (12 gm, 42.2 mmol) 10.2 g (Yield: 95%) of 2-(1-methyl-1H-imidazol-2-ylsulfanyl)-octanoic acid was isolated as colorless solid by following the procedure as outlined in example 9. MP: 95 C, MS: 257.1 (M+H)+.

Reference： [1]Patent: US6197791,2001,B1

30
[ 503039-46-1 ]
[ 60-56-0 ]
[ 1972-28-7 ]
{2-[4-(1-Methyl-imidazol-2-ylsulfanylmethyl)-benzoylamino]-phenyl}-carbamic Acid Tert-Butyl Ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With triphenylphosphine; In tetrahydrofuran; methanol; chloroform;	Step 4: {2-[4-(1-Methyl-imidazol-2-ylsulfanylmethyl)-benzoylamino]-phenyl}-carbamic Acid Tert-Butyl Ester (Compound 138) To a solution of <strong>[60-56-0]N-methyl-2-mercaptoimidazole</strong> (28 mg, 0.25 mmol) in THF (1 mL), at r.t. under N2 atmosphere were successively added 137 (70 mg, 0.20 mmol), triphenylphosphine (70 mg, 0.27 mmol) followed by dropwise addition of diethyl azodicarboxylate (48 muL, 0.31 mmol). The mixture was stirred for 2 h and the solvent was removed in vacuo. Purification by flash chromatography using MeOH/CHCl3 (5:95) as the eluent afforded the title compound 138 (81 mg), in 91% yield, which was found to contain some diethyl hydrazodicarboxylate residus. The compound was used as is without further purification.
91%	With triphenylphosphine; In tetrahydrofuran; methanol; chloroform;	Step 4: {2-[4-(1-Methyl-imidazol-2-ylsulfanylmethyl)-benzoylamino]-phenyl}-carbamic acid tert-butyl ester (compound 138) To a solution of <strong>[60-56-0]N-methyl-2-mercaptoimidazole</strong> (28 mg, 0.25 mmol) in THF (1 mL), at r.t. under N2 atmosphere were successively added 137 (70 mg, 0.20 mmol), triphenylphosphine (70 mg, 0.27 mmol) followed by dropwise addition of diethyl azodicarboxylate (48 muL, 0.31 mmol). The mixture was stirred for 2 h and the solvent was removed in vacuo. Purification by flash chromatography using MeOH/CHCl3 (5:95) as the eluent afforded the title compound 138 (81 mg), in 91% yield, which was found to contain some diethyl hydrazodicarboxylate residus. The compound was used as is without further purification.
91%	With triphenylphosphine; In tetrahydrofuran; methanol; chloroform;	Step 4: {2-[4-(1-Methyl-imidazol-2-ylsulfanylmethyl)-benzoylamino]-phenyl}-carbamic acid tert-butyl ester (Compound 138) To a solution of <strong>[60-56-0]N-methyl-2-mercaptoimidazole</strong> (28 mg, 0.25 mmol) in THF (1 mL), at r.t. under N2 atmosphere were successively added 137 (70 mg, 0.20 mmol), triphenylphosphine (70 mg, 0.27 mmol) followed by dropwise addition of diethyl azodicarboxylate (48 muL, 0.31 mmol). The mixture was stirred for 2 h and the solvent was removed in vacuo. Purification by flash chromatography using MeOH/CHCl3 (5:95) as the eluent afforded the title compound 138 (81 mg), in 91% yield, which was found to contain some diethyl hydrazodicarboxylate residus. The compound was used as is without further purification.

Reference： [1]Patent: US2004/142953,2004,A1
[2]Patent: US2005/288282,2005,A1
[3]Patent: US6897220,2005,B2

31
potassium borohydride [ No CAS ]
[ 3347-62-4 ]
[ 60-56-0 ]
K⁽¹⁺⁾*[HB(C₃H₂N₂(S)CH₃)2(C₃HN₂(CH₃)C₆H₅)]^(1-)=K[HB(C₃H₂N₂(S)CH₃)2(C₃HN₂(CH₃)C₆H₅)] [ No CAS ]

Reference： [1]European Journal of Inorganic Chemistry,2003,p. 2502 - 2511

32
[ 60-56-0 ]
[ 3840-30-0 ]
[ 847778-88-5 ]

Yield	Reaction Conditions	Operation in experiment
82%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 4h;	2-MERCAPTO-1-METHYLIMIDAZOLE (228.5 mg, 2 mmol), N, N-DIISOPROPYLETHYLAMINE (0.45 ML, 1.25 eq. ) and 3,4, 5-trimethoxybenzyl chloride (455 mg, 1.05 eq. ) were added to 2 ml dry DIMETHYLFORMAMIDE and the mixture was stirred at room temperature for 4 hours. The solvent was removed under reduced pressure and the residue was purified by MPFC (hexane/dichloromethane gradient) to give the desired 1-METHYL-2- (3, 4,5-trimethoxybenzylthio)-imidazole as a waxy, white solid in 82% yield, which was identified as compound 1. The structure of this compound was as follows:

Reference： [1]Patent: WO2005/23317,2005,A1 .Location in patent: Page/Page column 15

33
[ 591-50-4 ]
[ 60-56-0 ]
[ 79487-95-9 ]

Yield	Reaction Conditions	Operation in experiment
73%	With potassium phosphate; copper; In dimethyl sulfoxide; at 100℃; for 24h;	General procedure: A mixture of Cu0 powder (Sigma-Aldrich, <425mum, 99.5% trace metals basis, 0.095mg, 0.015mmol, 3-mol%), anhydrous K3PO4 (0.75mmol), 2-mercaptoimidazole/sulfur-containing azoles (0.5mmol), DMSO (0.2mL) and aryl halide (0.75mmol) were added to a reaction vial and a screw cap was fitted to it. The reaction mixture was stirred under air in a closed system at 100C for 24h. The heterogeneous mixture was subsequently cooled to room temperature and diluted with 4.0mL dichloromethane. The combined organic extracts were dried with anhydrous Na2SO4, filtered and the solvent was removed under reduced pressure. The crude product was loaded onto the column using minimal amounts of dichloromethane and was purified by silica-gel column chromatography to afford the S-arylated product. The identity and purity of products was confirmed by 1H and 13C NMR spectroscopic analys.

Reference： [1]European Journal of Organic Chemistry,2011,p. 1776 - 1781
[2]Chemical Communications,2010,vol. 46,p. 282 - 284
[3]Tetrahedron,2016,vol. 72,p. 6646 - 6653
[4]Angewandte Chemie - International Edition,2008,vol. 47,p. 2880 - 2883

34
[ 529-28-2 ]
[ 60-56-0 ]
[ 1032690-47-3 ]

Reference： [1]Angewandte Chemie - International Edition,2008,vol. 47,p. 2880 - 2883

35
[ 1005779-55-4 ]
[ 60-56-0 ]
[ 1005779-65-6 ]

Yield	Reaction Conditions	Operation in experiment
63%	With potassium carbonate; In N,N-dimethyl-formamide; at 180℃; for 0.138889h;Microwave irradiation;	Example 281; 2,5-dimethyl-N-{6-[(1-methyl-1H-imidazol-2-yl)thio]imidazo[1,2-b]pyridazin-2-yl}-3-furamide; [Show Image] A mixture of N-(6-chloroimidazo[1,2-b]pyridazin-2-yl)-2,5-dimethyl-3-furamide (29 mg, 0.1 mmol), 2-mercapto-1-methylimidazole (23 mg, 0.2 mmol), potassium carbonate (27 mg, 0.2 mmol) and N,N-dimethylformamide (2 mL) was stirred with heating at 180C for 500 sec in a microwave reaction apparatus. The reaction mixture was filtered, and the filtrate was purified by preparative HPLC to give the title compound (23.3 mg, 63%). LC-MS 369(M+H).

Reference： [1]Patent: EP2058309,2009,A1 .Location in patent: Page/Page column 174

36
[ 4225-92-7 ]
[ 60-56-0 ]
[ 1154952-09-6 ]

Yield	Reaction Conditions	Operation in experiment
97%	With triethylamine; In acetonitrile; at 20℃;	Et3N (0.239 mL, 0.98 mmol) was added to a solution of 2-bromo-l-(2,4,6-trimethyl- phenyl)-ethanone (208 mg, 0.86 mmol) and 2-mercapto-l-methylimidazole (98 mg, 0.86 mmol) in CH3CN (8 mL) at room temperature. The reaction was stirred overnight at room temperature then was quenched with of a saturated solution OfNH4Cl. The extraction was conducted with DCM (x2) then the organic phase was washed with brine and dried over MgSO4. The crude residue was the purified by flash chromatography (hexane/EtOAc 0- 40% gradient) to afford the expected compound (229 mg, 97%) as yellow oil. TLC single spot at R/ 0.23 (hexane/EtOAc 6:4); 1H NMR (270 MHz, CDCl3): delta 2.10 (s, 6H), 2.25 (s, 3H), 4.32 (s, 2H), 6.79 (s, 2H), 6.87 (s br, IH), 7.00 (s br, IH); LC/MS (APCI) m/z 275 (M++H); HPLC tr = 1.99 min (99.5%) in 10% water-acetonitrile.

Reference： [1]Patent: WO2009/106817,2009,A2 .Location in patent: Page/Page column 94

37
1-[1-(4-chlorophenyl)cyclobutyl]-2-bromoethanone [ No CAS ]
[ 60-56-0 ]
[ 1185752-14-0 ]

Yield	Reaction Conditions	Operation in experiment
76%	With triethylamine; In acetonitrile; at 20℃;	2-Mercapto-l-methylimidazole (83 mg, 0.73 mmol) was added neat to a solution of 2- bromo-l-[l-(4-chloro-phenyl)-cyclobutyl]-ethanone (210 mg, 0.73 mmol) in CH3CN (7 mL) at room temperature, then Et3N (0.203 mL, 1.46 mmol) was added neat to the mixture and the reaction was stirred overnight and over the next 4 days. The traces of thiol left were quenched by addition of a small spatula of resin 2-chlorotrityl chloride, stirred for Ih then the mixture was filtered and concentrated under vacuum. The crude mixture was purified by flash chromatography (hexane/EtOAc gradient 0-50%) to give the expected compound (179 mg, 76%) as yellow oil. TLC single spot at R/ 0.18 (hexane/EtOAc 5:5); 1H NMR (270 MHz, CDCl3): £ 1.74-1.92 (m, 2H), 2.29-2.44 (m, 2H), 2.69-2.84 (m, 2H), 3.59 (s, 3H), 3.84 (s, 2H), 6.85 (d, J = 1.2 Hz, IH), 6.96 (d, J = 1.2 Hz, IH), 7.13 (dt, J = 8.7, 2.5 Hz, 2H), 7.29 (dt, J = 8.7, 2.5 Hz, 2H); LC/MS (APCI) m/z 321 (M++H); Accurate Mass: Calculated (M+H)+ 321.0823; Found 321.0824; HPLC tr = 2.15 min (100%) in 10% water-acetonitrile.

Reference： [1]Patent: WO2009/106817,2009,A2 .Location in patent: Page/Page column 71

38
[ 99519-64-9 ]
[ 60-56-0 ]
[ 1185752-50-4 ]

Yield	Reaction Conditions	Operation in experiment
100%	With triethylamine; In acetonitrile; at 20℃;	2-Mercapto-l-methylimidazol (40.8 mg, 0.35 mmol) was neat to a solution of l-bromo-3- (4-chloro-phenyl)-3-methyl-butan-2-one (98.5 mg, 0.35 mmol) in CH3CN (5 mL) at room temperature, then Et3N (0.098 mL, 0.70 mmol) was added neat to the mixture and the reaction was stirred overnight. Thiol residues were trapped by addition of a small spatula of resin 2-chlorotrityl chloride in 30 min then the mixture was filtered and concentrated under vacuum. The crude mixture was purified by flash chromatography (hexane/EtOAc gradient 0-40%) to give the expected compound (108.5 mg, 100%) as brown solid. TLC single spot at R/ 0.47 (MeOH/DCM 1:9); Mp = [43.7-47.3 0C]; 1H NMR (270 MHz, CDCl3): delta 1.46 (s, 6H), 3.59 (s, 3H), 3.86 (s, 2H), 6.84 (d, J = 1.1 Hz, IH), 6.94 (d, J = 1.4 Hz, IH), 7.07-7.15 (m, 2H), 7.23-7.30 (m, 2H); Accurate Mass: calculated (MVH) 309.0823; found 309.0811; HPLC tr = 2.06 min (100%) in 10% water-acetonitrile.

Reference： [1]Patent: WO2009/106817,2009,A2 .Location in patent: Page/Page column 84

39
[ 1185023-08-8 ]
[ 60-56-0 ]
[ 1185751-91-0 ]

Yield	Reaction Conditions	Operation in experiment
97%	With triethylamine; In acetonitrile; at 20℃;	2-Mercapto-l-methylimidazole (84 mg, 0.73 mmol) was added neat to a solution of 2- bromo-l-[l-(4-chloro-phenyl)-cyclopropyl]-ethanone (200.5 mg, 0.73 mmol) in CH3CN (5 mL) at room temperature, then Et3N (0.203 mL, 1.46 mmol) was added neat to the mixture and the reaction was stirred over night. The reaction was then quenched by addition of a small spatula of resin 2-chlorotrityl chloride, stirred for IH then the mixture was filtered and concentrated under vacuum. The crude mixture was purified by flash chromatography (hexane/EtOAc gradient 0-50%) to afford the title compound (216.5 mg, 97%) as cream-yellow solid. TLC single spot at R/ 0.13 (hexane/EtOAc 7:3); Mp = [95.5- 97.0 0C]; 1H NMR (270 MHz, CDCl3): delta 1.19 (q, J = 3.7 Hz, 2H), 1.63 (q, J = 3.2 Hz, 2H), 3.62 (s, 3H), 3.86 (s, 2H), 6.87 (d, J = 1.2 Hz, IH), 6.98 (d, J = 1.2 Hz, IH), 7.32 (d, J = 0.7 Hz, 4H); LC/MS (APCI) m/z 307 (M++H); HPLC tr = 1.88 min (100%) in 10% water-acetonitrile.

Reference： [1]Patent: WO2009/106817,2009,A2 .Location in patent: Page/Page column 62

40
[ 1185133-42-9 ]
[ 60-56-0 ]
[ 1185752-38-8 ]

Yield	Reaction Conditions	Operation in experiment
95%	With triethylamine; In acetonitrile; at 20℃;	2-Mercapto-l-methylimidazole (72 mg, 0.63 mmol) was added neat to a solution of 2- bromo-l-[l-(4-chloro-phenyl)-cyclohexyl]-ethanone (200 mg, 0.63 mmol) in CH3CN (6 mL) at room temperature, then Et3N (0.177 mL, 1.27 mmol) was added neat to the mixture and the reaction was stirred for 36h. The traces of thiol left were quenched by addition of a small spatula of resin 2-chlorotrityl chloride, stirred for Ih then the mixture was filtered and concentrated under vacuum. The crude mixture was purified by flash chromatography (hexane/EtOAc gradient 0-50%) to give the expected compound (20 mg, 95%) as transparent oil. TLC single spot at R/ 0.2 (hexane/EtOAc 5:5); 1H NMR (270 MHz, CDCl3): £ 1.19-1.66 (m, 6H,), 1.73-1.87 (m, 2H), 2.23-2.36 (m, 2H), 3.56 (s, 3H), 3.90 (s, 2H), 6.82 (d, J = 1.4 Hz, IH), 6.91 (d, J = 1.4 Hz, IH), 7.13-7.20 (m, 2H), 7.22- 7.29 (m, 2H); LC/MS (APCI) m/z 349 (M+); HPLC tr = 2.80 min (>99%) in 10% water- acetonitrile.

Reference： [1]Patent: WO2009/106817,2009,A2 .Location in patent: Page/Page column 79

41
[ 1185134-09-1 ]
[ 60-56-0 ]
[ 1185752-39-9 ]

Yield	Reaction Conditions	Operation in experiment
90%	With triethylamine; In acetonitrile; at 20℃;	2-Mercapto-l-methylimidazole (57 mg, 0.50 mmol) was added neat to a solution of 2- bromo-l-[l-(4-chloro-phenyl)-cyclopentyl]-ethanone (150 mg, 0.50 mmol) in CH3CN (5 mL) at room temperature, then Et3N (0.139 mL, 1.00 mmol) was added neat to the mixture and the reaction was stirred overnight and over night. The traces of thiol left were quenched by addition of a small spatula of resin 2-chlorotrityl chloride, stirred for 30 min. then the mixture was filtered and concentrated under vacuum. The crude mixture was purified by flash chromatography (hexane/EtOAc gradient 0-40%) to give the expected compound (20 mg, 90%) as yellow oil. TLC single spot at R/ 0.2 (hexane/EtOAc 6:4); 1H NMR (270 MHz, CDCl3): delta 1.52-1.74 (m, 4H), 1.80-1.92 (m, 2H), 2.42-2.54 (m, 2H), 3.58 (s, 3H), 3.88 (s, 2H), 6.84 (d, J = 1.1 Hz, IH), 6.94 (d, J = 1.0 Hz, IH), 7.12-7.19 (m, 2H), 7.23-7.30 (m, 2H); LC/MS (APCI) m/z 335 (M+); HPLC tr = 2.60 min (>99%) in 10% water-acetonitrile.

Reference： [1]Patent: WO2009/106817,2009,A2 .Location in patent: Page/Page column 80

42
[ 497854-96-3 ]
[ 60-56-0 ]
7-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-N-[4-[[(1-methylimidazol-2-yl)sulfanyl]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of 7-[4-(2-butoxyethoxy)phenyl]-N-[4-(hydroxymethyl)phenyl]-1-isobutyl-2,3-dihydro-1-benzazepine-4-carboxamide (500 mg) in THF (10 ml) was added 1 droplet of pyridine, and thionyl chloride (0.09 ml) was added to the mixture at 0C. The mixture was allowed to be at room temperature under nitrogen atmosphere, and stirred for 1 hour. The solvent and excess thionyl chloride were distilled off under reduced pressure, and the residue was dissolved in THF (10 ml). This solution was added to a solution of 2-mercapto-1-methylimidazole (137 mg) and triethylamine (1.67 ml) in THF (10 ml) at 0C, and the mixture was heated overnight under nitrogen atmosphere at 50C. The mixture was allowed to be cooled, water was added to the mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (hexane:ethyl acetate = 1:2), to give 7-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-N-[4-[[(1-methylimidazol-2-yl)sulfanyl]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide (437 mg) (Compound 358) as yellow amorphous. 1H-NMR (200 MHz, CDCl3) delta 0.90 to 0.99 (9H, m), 1.30 to 1.45 (2H, m), 1.50 to 1.70 (2H, m), 1.95 to 2.20 (1H, m), 2.90 to 2.97 (2H, m), 3.19 (2H, d, J = 7.4 Hz), 3.28 (3H, s), 3.30 to 3.40 (2H, m), 3.55 (2H, t, J = 6.6 Hz), 3.80 (2H, t, J = 4.6 Hz), 4.13 to 4.18 (4H, m), 6.87 to 7.11 (7H, m), 7.37 to 7.56 (8H, m). Elemental Analysis for C38H46N4O3S·0.3H2O Calcd. C, 70.84; H, 7.29; N, 8.70; Found. C, 70.62; H, 7.49; N, 8.91.

Reference： [1]Patent: EP1422228,2004,A1 .Location in patent: Page 138-139

43
3-bromobenzo[b]selenophene-2-carboxylic acid ethyl ester [ No CAS ]
[ 60-56-0 ]
[ 1314236-08-2 ]

Yield	Reaction Conditions	Operation in experiment
68%	With aluminum oxide; potassium fluoride; 18-crown-6 ether; In acetonitrile; at 80℃; for 20h;	General procedure: A vial charged with 1 (0.25 g, 0.753 mmol), KF/Al2O3 (0.7 g) thiol (1.1 mmol), and 18-crown-6 (0.05 g, 0.225 mmol) in 5 mL of acetonitrile was heated for 20 h at 80 C. Then solvent was evaporated under reduced pressure and crude product was purified by flash chromatography on silica gel using the mixture petroleum ether - ethylacetate as eluent.

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3434 - 3443

44
[ 60-56-0 ]
[ 16681-59-7 ]

Reference： [1]Dalton Transactions,2011,vol. 40,p. 11382 - 11384

45
bis(((difluoromethyl)sulfinyl)oxy)zinc [ No CAS ]
[ 60-56-0 ]
[ 1355729-66-6 ]

Yield	Reaction Conditions	Operation in experiment
69%	With tert.-butylhydroperoxide; trifluoroacetic acid; In dichloromethane; water; for 16h;	General procedure: Difluoromethylation of Heterocycles Standard Procedures: Procedure B: To a solution of heterocycle (0.25 mmol, 1.0 equiv) and zinc difluoromethanesulfinate (DFMS) (173 mg, 0.50 mmol, 2.0 equiv ?calculated as anhydrous?) in dichloromethane (1.0 mL) and water (0.4 rnL) at room temperature was added trifluoroacetic acid (20 muL, 0.25 rnmol, 1.0 equiv) followed by slow addition of tert-butyl hydroperoxide (70% solution in water, 0.1 mL, 0.75 mmol, 3.0 equiv) with vigorous stirring. The reaction was monitored by thin layer chromatography until completion. For substrates which do not go to completion in 24 hours, a second addition of DFMS (2.0 equiv) and tert-butyl hydroperoxide (3.0 equiv) may be added to drive the reaction further. Upon consumption of starting material, the reaction was partitioned between dichioromethane (2.0 mL) and saturated sodium bicarbonate (2.0 mL) . The organic layer was separated, and the aqueous layer was extracted with dichioromethane (3 X 2.0 mL) . The organic layers were dried with sodium sulfate, concentrated and purified by column chromatography on silica gel. If substrates are less reactive, alpha,alpha,-trifluorotoluene can be substituted for DCM, as it causes improved reactivity for some cases. For water-soluble starting materials, a purely aqueous reaction (1.0 mL of water) can be run and in some cases, it was also found to display improved reactivity. In lieu of a workup, these reactions can be concentrated and the product purified directly. If the addition of tert-butyl hydroperoxide is performed too rapidly, the resulting exotherm can result in reduced yield and selectivity. This is especially important on larger scales (see gram scale procedure: substrate 2), where a syringe pump can be used to meter in tert-butyl hydroperoxide.It is noted that trifluoroacetic acid (TFA) is not required in either of the above procedures. It was also found that TFA showed improved rate and conversion for selected nitrogen heteroarene substrates, but was not essential to achieve the desired reactivity for most cases. When present, TFA is typically used at about 0.25 to about 2 equivalents per equivalent of nitrogen heteroarene, and more preferably at about 0.5 to about 1.5 equivalents relative to the nitrogen heteroarene.

Reference： [1]Journal of the American Chemical Society,2012,vol. 134,p. 1494 - 1497
[2]Patent: WO2013/82028,2013,A1 .Location in patent: Page/Page column 21; 22; 42

46
[ 590-92-1 ]
[ 60-56-0 ]
2-(2-carboxyethylthio)-1-methyl-1H-imidazol-1-ium bromide [ No CAS ]

Reference： [1]Synthetic Communications,2013,vol. 43,p. 1 - 8

47
[ 214210-21-6 ]
[ 60-56-0 ]
[ 1093966-87-0 ]

Yield	Reaction Conditions	Operation in experiment
13%		To a dichloromethane solution (20 mL) of (3-cyano-4- fluorophenyl)boronic acid (660 mg) were added 1-methyl-lH- imidazole-2-thiol (913 mg) , copper(II) acetate (1.45 g) and pyridine (1 mL) , and the mixture was stirred at room temperature for 3 days. The insoluble materials were removed by filtration. The filtrate was diluted with ethyl acetate and water. The organic layer was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by NH-silica gel column chromatography (eluate: ethyl acetate) to give a yellow oily substance. The obtained a yellow oily substance was dissolved in 1-butanol (10 mL) , hydrazine monohydrate (0.5 mL) was added, and the mixture was stirred at 1300C for 4 hr. The reaction mixture was concentrated, and washed with diluted with ethyl acetate and water. The organic layer was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give the title compound (120 mg, yield 13%) <n="204"/>as pale-yellow crystals. Melting point 174C.

Reference： [1]Patent: WO2008/156757,2008,A1 .Location in patent: Page/Page column 202-203

48
Ni(II)-(S)-BPB-D-Ala [ No CAS ]
[ 60-56-0 ]
C₃₂H₃₁N₅NiO₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With potassium carbonate; In acetonitrile; at 20 - 25℃; for 8h;	General procedure: To a solution of complex 1 in MeCN were added K2CO3 and nucleophiles 2a-f at 20-25 C with stirring. The reaction was monitored by TLC (SiO2, ???l3/acetone = 3:1) following the disappearance of the spot of the initial complex 1. Upon completion of the reaction, the mixture was filtered, the K2??3 precipitate was washed with CH3CN and the solution was evaporated. A small part of the dry residue (?1 g) was purified by chromatography on SiO2 (???l3/acetone = 3:1, 20 × 20 cm) to isolate the diastereoisomerically pure complexes 3a-f. The products were crystallized from methanol.

Reference： [1]Tetrahedron Asymmetry,2013,vol. 24,p. 229 - 232

49
[ 66-71-7 ]
copper(II) choride dihydrate [ No CAS ]
[ 60-56-0 ]
[Cu(methimazole)₂(1,10-phenanthroline)(H₂O)₂]Cl₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	In ethanol; water; at 20℃; for 2h;	[Cu(MeimzH)2(phen)(H2O)2]Cl2 (Cu-Met-phen) a solution was prepared by mixing 1 mmol (0.1142 g) of methimazole dissolved in 5 mL of water with 1 mmol (0.1802 g) of o-phenanthroline dissolved in 5 mL of ethanol. To this solution, 1 mmol (0.1705 g) of solid copper(II) chloride dihydrate was slowly added under continuous stirring. The resulting mixture was stirred at room temperature for 2 h. After that, a light green precipitate was formed which was separated, filtered and washed several times with ethanol. After this procedure it was dried in an oven at 60 C. Anal. Calc. for C20H24N6O2S2Cl2Cu: C, 41.48; H, 4.15; N, 14.52; S, 11.06. Found: C, 41.15; H, 4.27; N, 14.78; S, 11.38 %. Yield:75%.

Reference： [1]Inorganica Chimica Acta,2013,vol. 405,p. 243 - 251

50
[ 60-56-0 ]
[ 762-21-0 ]
diethyl 2-(1-methylimidazol-2-yl-sulfanyl)fumarate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With pyridine; In dichloromethane; at 20℃; for 2h;	General procedure: A mixture of pyridine (1 mmol) in 3 mL dichloromethane was added dropwise to a magnetically stirred solution of 2-mercapto-1-methylimidazole or 5-mercapto-1-methyltetrazole (1 mmol) and acetylenic esters (1 mmol) in 15 mL dichloromethane. The reaction mixture was then stirred for 2 h at room temperature. The solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography using hexane-ethyl acetate as eluent. The solvent was removed under reduced pressure to afford the product.

Reference： [1]Journal of Chemical Research,2013,vol. 37,p. 523 - 525

51
[ 66086-33-7 ]
[ 60-56-0 ]
di-tert-butyl 2-(1-methylimidazol-2-yl-sulfanyl)fumarate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With pyridine; In dichloromethane; at 20℃; for 2h;	General procedure: A mixture of pyridine (1 mmol) in 3 mL dichloromethane was added dropwise to a magnetically stirred solution of 2-mercapto-1-methylimidazole or 5-mercapto-1-methyltetrazole (1 mmol) and acetylenic esters (1 mmol) in 15 mL dichloromethane. The reaction mixture was then stirred for 2 h at room temperature. The solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography using hexane-ethyl acetate as eluent. The solvent was removed under reduced pressure to afford the product.

Reference： [1]Journal of Chemical Research,2013,vol. 37,p. 523 - 525

52
[ 762-42-5 ]
[ 60-56-0 ]
dimethyl 2-(1-methylimidazol-2-yl-sulfanyl)fumarate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With pyridine; In dichloromethane; at 20℃; for 2h;	General procedure: A mixture of pyridine (1 mmol) in 3 mL dichloromethane was added dropwise to a magnetically stirred solution of 2-mercapto-1-methylimidazole or 5-mercapto-1-methyltetrazole (1 mmol) and acetylenic esters (1 mmol) in 15 mL dichloromethane. The reaction mixture was then stirred for 2 h at room temperature. The solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography using hexane-ethyl acetate as eluent. The solvent was removed under reduced pressure to afford the product.

Reference： [1]Journal of Chemical Research,2013,vol. 37,p. 523 - 525

53
[ 24424-99-5 ]
[ 60-56-0 ]
[ 1607462-50-9 ]

Yield	Reaction Conditions	Operation in experiment
89%	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 0.5h;Inert atmosphere;	Figure 1 shows the structures and synthetic pathways of methimazole derivatives. Briefly, compound 3 (3) was prepared through the reaction of an MMI (compound 2; 2) (400 mg, 3.5 mmol) and potassium carbonate (968 mg, 7 mmol) in 7 mL of N,N-dimethylformamide and the subsequently di-tert-butyl dicarbonate (1.1 mL, 5.2 mmol) was added. The reaction mixture was stirred at 60 C for 30 min in an N2 atmosphere. The resulting mixture was partitioned between ethyl acetate (40 mL) and H2O (20 mL). The organic layer was washed with brine (20 mL), dried over MgSO4, and then concentrated in vacuo. The residue was separated by chromatography over silica gel and eluted with hexane/ethyl acetate (1:1) to afford 665 mg (89% yield) of 3.
89%	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 0.5h;Inert atmosphere;	2-mercapto-1-methylimidazole (400 mg, 3.5 mmol) was mixed with K2CO3 (968 mg, 7 mmol) in N, N-dimethylformamide (N, N-dimethylformamide ) (7 mL), followed by addition of di-tert-butyl dicarbonate (1.1 mL, 5.2 mmol). The resulting mixture was then stirred at 60 C for 30 minutes in a nitrogen atmosphere, followed by partitioning with ethyl acetate (40 mL) and water (20 mL). The ethyl acetate layer was then collected and washed with brine (brine), dried over anhydrous MgSO4, and then concentrated under vacuum. Thereafter, the resulting residue was purified by silica gel column chromatography to give a compound (665 mg, yield 89%) as a pale yellow solid.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 2809 - 2815
[2]Patent: TW2016/7932,2016,A .Location in patent: Paragraph 0056

54
[ 1219200-16-4 ]
[ 60-56-0 ]
[ 1607462-51-0 ]

Yield	Reaction Conditions	Operation in experiment
87%	With potassium carbonate; In N,N-dimethyl-formamide; at 70℃; for 1h;Inert atmosphere;	Compound 4 (4) was prepared through the reaction of a mixture of 2 (1.12 g, 9.8 mmol) and methyl 3-bromo-2-[(tert-butoxycarbonyl)-amino]propanoate (2.79 g, 9.8 mmol) in 35 mL of N,N-dimethylformamide and the subsequently potassium carbonate (2.71 g, 19.6 mmol) was added. The reaction mixture was stirred at 70 C for 1 h in an N2 atmosphere. The resulting mixture was filtered and concentrated in vacuo. The residue was separated with chromatography over silica gel and eluted with hexane/ethyl acetate (3:7) to afford 2.60 g (87% yield) of 4.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 2809 - 2815

55
[ 154057-56-4 ]
[ 60-56-0 ]
2-cyclopropyl-4-(4-fluorophenyl)-3-[(1-methyl-1H-imidazol-2-ylthio)methyl]quinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%		General procedure: Aq 1 M NaOH (9 mL, 1.5 equiv) was added to a stirred MeOH (20mL) solution of the appropriate aromatic thiol (7.2 mmol, 1.2equiv). The solution was stirred at r.t. for 15 min and then the heterocyclicalkyl bromide 2 or 3 (6 mmol, 1 equiv) was added. When rosuvastatin moiety bromides 2 were used, THF (10 mL) was also added to the mixture to improve solubility. After 18 h, the solvent was evaporated, the residue was dissolved in CH2Cl2 (50 mL), and washed with H2O (100 mL). The aqueous phase was additionally extracted with CH2Cl2 (2 × 25 mL). The combined organic phases were dried (MgSO4) and the solvent was evaporated. The residuewas recrystallized and the isolated product was dried in vacuumovernight at 60 C below 50 mbar to give the pure sulfide heterocyclic precursor 4 or 5 in 75-97% yield.

Reference： [1]Synthesis,2014,vol. 46,p. 2333 - 2346

56
[ 799842-07-2 ]
[ 60-56-0 ]
N-{4-(4-fluorophenyl)-6-isopropyl-5-[(1-methyl-1H-imidazol-2-ylthio)methyl]pyrimidin-2-yl}-N-methylmethanesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%		General procedure: Aq 1 M NaOH (9 mL, 1.5 equiv) was added to a stirred MeOH (20mL) solution of the appropriate aromatic thiol (7.2 mmol, 1.2equiv). The solution was stirred at r.t. for 15 min and then the heterocyclicalkyl bromide 2 or 3 (6 mmol, 1 equiv) was added. When rosuvastatin moiety bromides 2 were used, THF (10 mL) was also added to the mixture to improve solubility. After 18 h, the solvent was evaporated, the residue was dissolved in CH2Cl2 (50 mL), and washed with H2O (100 mL). The aqueous phase was additionally extracted with CH2Cl2 (2 × 25 mL). The combined organic phases were dried (MgSO4) and the solvent was evaporated. The residuewas recrystallized and the isolated product was dried in vacuumovernight at 60 C below 50 mbar to give the pure sulfide heterocyclic precursor 4 or 5 in 75-97% yield.

Reference： [1]Synthesis,2014,vol. 46,p. 2333 - 2346

57
[ 934-37-2 ]
[ 60-56-0 ]
C₁₃H₁₄N₄S [ No CAS ]