57090-88-7|1H-Imidazole-4-carbonitrile| Ambeed

Structure of 4-Cyanoimidazole
CAS No.: 57090-88-7

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Quality Control of [ 57090-88-7 ] Purity: 98% SDS Specification

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Product Details of [ 57090-88-7 ]

CAS No. :	57090-88-7
Formula :	C₄H₃N₃
M.W :	93.09
SMILES Code :	N#CC1=CNC=N1
MDL No. :	MFCD00233358
InChI Key :	NWVGXXPWOYZODV-UHFFFAOYSA-N
Pubchem ID :	564457

Safety of [ 57090-88-7 ]

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

Computational Chemistry of [ 57090-88-7 ] Show Less

Physicochemical Properties

Num. heavy atoms	7
Num. arom. heavy atoms	5
Fraction Csp3	0.0
Num. rotatable bonds	0
Num. H-bond acceptors	2.0
Num. H-bond donors	1.0
Molar Refractivity	23.3
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	52.47 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.62
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	0.11
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	0.28
Log P_o/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.	-1.44
Log P_o/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	1.02
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	0.12

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.02
Solubility	8.99 mg/ml ; 0.0966 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.	-0.77
Solubility	15.9 mg/ml ; 0.171 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	-1.23
Solubility	5.49 mg/ml ; 0.059 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.	-6.79 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)	1.66

Application In Synthesis of [ 57090-88-7 ]

* 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 [ 57090-88-7 ]

[ 57090-88-7 ] Synthesis Path-Downstream 1~41

1
[ 56745-98-3 ]
[ 57090-88-7 ]

References: [1]Journal of Heterocyclic Chemistry,1983,vol. 20,p. 1103 - 1106.

2
[ 103-71-9 ]
[ 57090-88-7 ]
[ 87864-82-2 ]

References: [1]Journal of Heterocyclic Chemistry,1983,vol. 20,p. 1103 - 1106.

3
[ 624-83-9 ]
[ 57090-88-7 ]
[ 87864-83-3 ]

References: [1]Journal of Heterocyclic Chemistry,1983,vol. 20,p. 1103 - 1106.

4
[ 624-83-9 ]
[ 57090-88-7 ]
[ 87864-89-9 ]

References: [1]Journal of Heterocyclic Chemistry,1983,vol. 20,p. 1103 - 1106.

5
[ 33468-69-8 ]
[ 57090-88-7 ]

References: [1]Journal of Organic Chemistry,1986,vol. 51,p. 3228 - 3231.

6
[ 57090-88-7 ]
[ 156440-99-2 ]
[ 156442-40-9 ]

References: [1]Bioorganic and Medicinal Chemistry,1999,vol. 7,p. 1665 - 1682.

8
[ 693-03-8 ]
[ 57090-88-7 ]
1-[1H-imidazol-4⁽⁵⁾-yl]pentan-1-one [ No CAS ]

References: [1]Synthesis,2003,p. 677 - 680.

9
[ 926-62-5 ]
[ 57090-88-7 ]
1-[1H-imidazol-4⁽⁵⁾-yl]-3-methylbutan-1-one [ No CAS ]

References: [1]Synthesis,2003,p. 677 - 680.

10
[ 925-90-6 ]
[ 57090-88-7 ]
1-(1H-imidazol-4-yl)-1-propanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With sodium hydroxide; sulfuric acid; In tetrahydrofuran; hexane; water;	Example 3 Production of 1-(1H-imidazol-4-yl)-1-propanone A solution of <strong>[57090-88-7]4-cyanoimidazole</strong> (2 g, 21.4 mmol) in THF (25 ml) was added dropwise to a solution (68.5 mL, 68.5 mmol, 3.2 equivalents) of 1 M ethyl magnesium bromide in THF at 0 to 10°C under a nitrogen atmosphere. The mixture was stirred at 15 to 25°C for 4 h. Water (20 ml) and 10percent aqueous sulfuric acid solution (45 ml) were successively added dropwise, and the mixture was stirred for 1 h. A 30percent aqueous sodium hydroxide solution was added dropwise to adjust the pH to 8. After partitioning, the aqueous layer was extracted with ethyl acetate (15 ml * 2). The organic layer was combined, and the mixture was washed successively with saturated aqueous sodium hydrogencarbonate and saturated brine, and concentrated under reduced pressure. The concentration residue was broken up with n-hexane (6 ml), and the crystals were collected by filtration and washed with n-hexane. The crystals were dried in vacuo (40°C) to give 1-(1H-imidazol-4-yl)-1-propanone (1.68 g, yield 63percent). 1H-NMR (CDCl3): delta1.06(3H, t, J = 7.4 Hz), 2.86(2H, q, J = 7.4 Hz), 7.81(1H, s), 7.84(1H, s)

References: [1]Synthesis,2003,p. 677 - 680.
[2]Patent: EP1193258,2002,A1 .

11
[ 927-77-5 ]
[ 57090-88-7 ]
1-[1H-imidazol-4⁽⁵⁾-yl]butan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With sodium hydroxide; sulfuric acid; In tetrahydrofuran; hexane; water;	Example 4 Production of 1-(1H-imidazol-4-yl)-1-butanone A solution of <strong>[57090-88-7]4-cyanoimidazole</strong> (2 g, 21.4 mmol) in THF (25 ml) was added dropwise to a solution (68.5 mL, 68.5 mmol, 3.2 equivalents) of 1 M n-propyl magnesium bromide in THF at 0to 10°C under a nitrogen atmosphere. The mixture was stirred at 15 to 25°C for 4 h. Water (20 ml) and 10percent aqueous sulfuric acid solution (45 ml) were successively added dropwise, and the mixture was stirred at 1 h. A 30percent aqueous sodium hydroxide solution was added dropwise to adjust the pH to 8. After partitioning, the aqueous layer was extracted with ethyl acetate (15 ml * 2). The organic layer was combined, and the mixture was washed successively with saturated aqueous sodium hydrogencarbonate and saturated brine, and concentrated under reduced pressure. The concentration residue was broken up with n-hexane (12 ml), and the crystals were collected by filtration and washed with n-hexane. The crystals were dried in vacuo (40°C) to give 1-(1H-imidazol-4-yl)-1-butanone (2.45 g, yield 83percent). 1H-NMR (CDCl3): delta0.90(3H, t, J=7.4Hz), 1.60(2H, q, J=7.3Hz), 3.34(2H, q, J=7.1Hz), 7.77(1H, s), 7.85(1H, s)

References: [1]Synthesis,2003,p. 677 - 680.
[2]Patent: EP1193258,2002,A1 .

12
[ 671795-46-3 ]
[ 57090-88-7 ]
1-[1H-imidazol-4⁽⁵⁾-yl]-2-methylbutan-1-one [ No CAS ]

References: [1]Synthesis,2003,p. 677 - 680.

13
[ 57090-88-7 ]
[ 75-26-3 ]
[ 247174-71-6 ]

References: [1]Synthesis,2003,p. 677 - 680.

14
[ 57090-88-7 ]
[ 931-50-0 ]
cyclohexyl[1H-imidazol-4⁽⁵⁾-yl]methanone [ No CAS ]

References: [1]Synthesis,2003,p. 677 - 680.

15
[ 57090-90-1 ]
[ 57090-88-7 ]

Yield	Reaction Conditions	Operation in experiment
81%	With acetic anhydride; at 20 - 100℃; for 1h;	(2) Step will be viscous [...] 4 - a hydroxyimino imidazole (0.227 muM), adding acetic anhydride 69.5 g (0.681 muM), the states the dehydration reaction the reaction condition is: 4 - a hydroxyimino imidazole, acetic anhydride molar ratio of 1:3, raising the temperature to 100 C, thermal insulation reaction 1 hours, reduced pressure distillation acetic anhydride, after the end of the distillation, control temperature ? 30 C dropwise 25% of sodium hydroxide aqueous solution to adjust the pH value of 8.0, then adding ethyl acetate extraction twice, extraction layers to mix and then adding 25% sodium chloride aqueous solution washing two times, after washing the oil be reduced pressure distillation ethyl acetate, then adding toluene dehydration, after the completion of the dehydration in toluene on a large number of solid precipitation, filtration, the filter cake and dichloromethane is used for washing, drying to obtain the 17.6g1H - imidazole -4 - carbonitrile content of 97%, yield 81%.
		A 22-L, four-neck, round-bottom flask equipped with a mechanical stirrer, a temperature probe, a condenser, and an addition funnel with a nitrogen inlet was charged with lH-imidazole-4-carboxaldehyde (Aldrich, 1.10 kg, 11.5 mol) and pyridine (3.0 L, 3.0 mol). The reaction flask was cooled to 8 C with an ice bath and hydroxylamine hydrochloride (871 g, 12.5 mol) was added slowly in portions to maintain the internal temperature below 30 C. The reaction was allowed to cool to ambient temperature and stirred for 2 h at ambient temperature. The resulting thick yellow solution was heated to 80 C with a heating mantle and acetic anhydride (2.04 L, 21.6 mol) was added dropwise over 200 min to maintain the temperature below 110 0C during the addition. The reaction EPO <DP n="132"/>mixture was heated at 100 0C for 30 min, after which time it was allowed to cool to ambient temperature and then further cooled in an ice bath. The pH was adjusted to 8.0 (pH meter) by the addition of 25 wt % NaOH (5.5 L) at such a rate that the internal temperature was maintained below 30 C. The reaction mixture was then transferred into a 22-L separatory funnel and extracted with ethyl acetate (6.0 L). The combined organic layer was washed with brine (2 x 4.0 L), dried over MgSO4, filtered, and concentrated to dryness under reduced pressure at 35 0C to give the crude product as a yellow semisolid. The resulting semisolid was suspended in toluene (3.0 L) and stirred for 1 h, after which time it was filtered to give a light yellow solid, which was resuspended in toluene (3.0 L) and stirred for 1 h. The resulting slurry was filtered and the filter cake washed with toluene (2 x 500 mL) to give the title compound as a light yellow solid [870 g, 82%). The 1H and 13C NMR spectra were consistent with the assigned structure.
	With pyridine; acetic anhydride; at 120℃; for 1.5h;	15.0 g (156 mmol) 4-formyl-1H-imidazole in 100 ml of pyridine are combined with 12.5 g (180 mmol) hydroxylamine-hydrochloride at 60 C. with stirring and the mixture is stirred at 60 C. for 1.25 h. Then the mixture is heated to 80 C. and 28.0 ml (297 mmol) acetic anydride are added such that the temperature remains between 80 and 120 C. After removal of the heating bath stirring is continued for a further 1.5 h during the cooling and the mixture is then evaporated down i. vac. The residue is mixed with ice and neutralised with 10n sodium hydroxide solution. The mixture is extracted with ethyl acetate and the combined organic phases are washed with semisat. and sat. sodium chloride solution, dried on magnesium sulphate and evaporated down i. vac. The residue is taken up twice in toluene and in dichloromethane and in each case evaporated down completely. Then the residue is triturated in diethyl ether, filtered and washed with a little diethyl ether and dried. Yield: 12.22 g (127.3 mmol, 82%) C4H3N3 (93.09) Mass spectrum: (M+H)+=94

References: [1]Patent: CN109336820,2019,A .Location in patent: Paragraph 0032; 0037; 0038.
[2]Synthesis,2003,p. 677 - 680.
[3]Patent: WO2006/47277,2006,A2 .Location in patent: Page/Page column 130-131.
[4]Patent: US2008/51578,2008,A1 .Location in patent: Page/Page column 48.
[5]Organic Process Research and Development,2007,vol. 11,p. 206 - 209.

16
[ 75-16-1 ]
[ 57090-88-7 ]
[ 61985-25-9 ]

Yield	Reaction Conditions	Operation in experiment
48%		(b) 4-acetyl-1H-imidazole 1.42 g (15.3 mmol) <strong>[57090-88-7]4-cyano-1H-imidazole</strong> are combined with 11.2 ml (33.6 mmol) 3n ethereal methyl-magnesium-bromide solution with 25 ml THF in 75 ml THF at 10° C. with cooling in the ice bath and after removal of the ice bath the mixture is stirred for another 2.5 h at ambient temperature. After the addition of another 3.5 ml (10.5 mmol) 3n ethereal methyl-magnesium bromide solution and stirring for 15 min at ambient temperature, 45 ml of 1m sulphuric acid are added and the mixture is stirred for 30 min. After the addition of 20 ml of 10n sodium hydroxide solution the organic phase is separated off, the aqueous phase is saturated with sodium chloride and extracted with ethyl acetate. The combined organic phases are dried on magnesium sulphate and evaporated down i. vac. Yield: 48percent C5H6N2O (110.11) Mass spectrum: (M+H)+=111

References: [1]Patent: US2008/51578,2008,A1 .Location in patent: Page/Page column 48.

17
[ 706817-64-3 ]
[ 57090-88-7 ]
1-(6-cyclohexyl-2-oxo-2H-pyrane-4-yl)-1H-imidazole-4-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34%	With potassium carbonate; potassium iodide; In acetonitrile; for 4h;Heating / reflux;	4-Bromo-6-cyclohexyl-pyrane-2-one (915mg, 3.56mmol) and LH-IMIDAZOLE-4- carbonitrile (276mg, 2. 96mmol) were dissolved in acetonitrile (20mL) in a 100mL flask. After K2CO3 (1.23g, 8. 88MMOL) and KI (9LMG, 10percent w/w) were added thereto, the reaction solution was heated under reflux. After 4 hours, the reaction solution was cooled down to room temperature and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel using MC: MEOH (20: 1) as eluent. The fractions containing the product were combined and evaporated to give a white solid (271mg, 34percent). APOS;H-NMR (CDC13) ; 5 = 7.99 (s, 1H), 7.86 (s, 1H), 7.68 (d, 1H), 7.63 (d, 1H), 2.55 (m, 1H), 2.1-1. 2 (m, LOH). MS (ESI); 270 (M++I).

References: [1]Patent: WO2004/50624,2004,A1 .Location in patent: Page 60.

18
[ 76513-69-4 ]
[ 57090-88-7 ]
[ 854044-50-1 ]

Yield	Reaction Conditions	Operation in experiment
70%	With potassium carbonate; In acetone; at 20℃; for 10h;	A flask charged with <strong>[57090-88-7]imidazole-4-carbonitrile</strong> (0.5 g, 5.2 mmol) {Synthesis, 677, 2003), 2-(trimethylsilyl)ethoxymethyl chloride (SEMCl) (0.95 mL, 5.3 mmol), K2CO3 EPO <DP n="43"/>(1.40 g, 10.4 mmol), and acetone (5 mL) was stirred for 1O h at RT. The mixture was diluted with EtOAc (20 mL) and washed with water (20 mL) and brine (20 mL) and the organic layer dried over MgSO4. The crude product was eluted from a 20-g SPE cartridge (silica) with 30 percent EtOAc/hexane to give 0.80 g (70 percent) of the title compound as a colorless oil. Mass spectrum (CI (CH4), m/z) Calcd. for Ci0Hi7N3OSi, 224.1 (M+H), found 224.1.
70%	With potassium carbonate; In acetone; at 20℃; for 10h;Product distribution / selectivity;	Example 34-Cyano-l-(2-trimethylsilanyl-ethoxymethyl)-lH-imidazole-2-carboxyIate potassium salt; EPO <DP n="38"/> a) 1 -(2-Trimethylsilanyl-ethoxymethyl)- 1 H-<strong>[57090-88-7]imidazole-4-carbonitrile</strong> A flask charged with <strong>[57090-88-7]imidazole-4-carbonitrile</strong> (0.50 g, 5.2 mmol) (Synthesis, 677(2003)) 2-(trimethylsilyl)ethoxymethyl chloride (SEMCl) (0.95 mL, 5.3 mmol), K2CO3 (1.40 g, 10.4 mmol), and acetone (5 mL) was stirred for 10 h at RT. The mixture was diluted with EtOAc (20 mL) and washed with water (20 mL) and brine (20 mL) and the organic layer dried over MgSO4. The crude product was eluted from a 20-g SPE cartridge (silica) with 30 percent EtOAc/hexane to give 0.80 g (70 percent) of the title compound as a colorless oil. Mass spectrum (CI (CH4), m/z) Calcd. for C10Hi7N3OSi, 224.1 (M+H), found 224.1.
70%	With potassium carbonate; In acetone; at 20℃; for 10h;	A flask charged with <strong>[57090-88-7]imidazole-4-carbonitrile</strong> (0.5 g, 5.2 mmol) (Synthesis, 677, 2003), 2-(trimethylsilyl)ethoxymethyl chloride (SEMCl) (0.95 mL, 5.3 mmol), K2CO3 (1.40 g, 10.4 mmol), and acetone (5 mL) was stirred for 10 h at RT. The mixture was diluted with EtOAc (20 mL) and washed with water (20 mL) and brine (20 mL) and the organic layer dried over MgSO4. The crude product was eluted from a 20-g SPE cartridge (silica) with 30percent EtOAc/hexane to give 0.80 g (70percent) of the title compound as a colorless oil. Mass spectrum (CI(CH4), m/z) Calcd. for C10H17N3OSi, 224.1 (M+H), found 224.1.

70%	With potassium carbonate; In acetone; at 20℃; for 10h;	A flask charged with <strong>[57090-88-7]imidazole-4-carbonitrile</strong> (0.50 g, 5.2 mmol) (Synthesis, 677, 2003), 2-(trimethylsilyl)ethoxymethyl chloride (SEMCl) (0.95 mL, 5.3 mmol), K2CO3 (1.40 g, 10.4 mmol), and acetone (5 mL) was stirred for 10 h at RT. The mixture was diluted with ethyl acetate (EtOAc) (20 mL) and washed with water (20 mL) and brine (20 mL) and the organic layer was dried over MgSO4. The crude product was eluted from a 20-g SPE cartridge (silica) with 30percent EtOAc/hexane to give 0.80 g (70percent) of the title compound as a colorless oil. Mass spectrum (CI (CH4), m/z) Calcd. for C10H17N3OSi, 224.1 (M+H), found 224.1.
70%	With potassium carbonate; In acetone; at 20℃; for 10h;	a) 1-(2-Trimethylsilanyl-ethoxymethyl)-<strong>[57090-88-7]1H-<strong>[57090-88-7]imidazole-4-carbonitrile</strong></strong> A flask charged with <strong>[57090-88-7]imidazole-4-carbonitrile</strong> (0.50 g, 5.2 mmol) (Synthesis, 677, 2003), 2-(trimethylsilyl)ethoxymethyl chloride (SEMCl) (0.95 mL, 5.3 mmol), K2CO3 (1.40 g, 10.4 mmol), and acetone (5 mL) was stirred for 10 h at RT. The mixture was diluted with ethyl acetate (EtOAc) (20 mL) and washed with water (20 mL) and brine (20 mL) and the organic layer dried over MgSO4. The crude product was eluted from a 20-g SPE cartridge (silica) with 30percent EtOAc/hexane to give 0.80 g (70percent) of the title compound as a colorless oil: Mass spectrum (CI (CH4), m/z) Calcd. for C10H17N3OSi, 224.1 (M+H), found 224.1.
70%	With potassium carbonate; In acetone; at 20℃; for 10h;	A flask charged with <strong>[57090-88-7]imidazole-4-carbonitrile</strong> (0.50 g, 5.2 mmol) (Synthesis, 677, 2003), 2-(trimethylsilyl)ethoxymethyl chloride (SEMCl) (0.95 mL, 5.3 mmol), K2CO3 (1.40 g, 10.4 mmol), and acetone (5 mL) was stirred for 10 h at RT. The mixture was diluted with EtOAc (20 mL), washed with water (20 mL), brine (20 mL) and the organic layer was dried over MgSO4. The crude product was eluted from a 20-g SPE cartridge (silica) with 30percent EtOAc/hexane to give 0.80 g (70percent) of the title compound as a colorless oil. Mass spectrum (CI (CH4), m/z): Calcd. for C10H17N3OSi, 224.1 (M+H), found 224.1.
70%	With potassium carbonate; In acetone; at 20℃; for 10h;	a) 1-(2-Trimethylsilanyl-ethoxymethyl)-<strong>[57090-88-7]1H-<strong>[57090-88-7]imidazole-4-carbonitrile</strong></strong> A flask charged with <strong>[57090-88-7]imidazole-4-carbonitrile</strong> (0.5 g, 5.2 mmol) (Synthesis, 677, 2003), 2-(trimethylsilyl)ethoxymethyl chloride (SEMCl) (0.95 mL, 5.3 mmol), K2CO3 (1.40 g, 10.4 mmol), and acetone (5 mL) was stirred for 10 h at RT. The mixture was diluted with EtOAc (20 mL) and washed with water (20 mL) and brine (20 mL) and the organic layer dried over MgSO4. The crude product was eluted from a 20-g SPE cartridge (silica) with 30percent EtOAc/hexane to give 0.80 g (70percent) of the title compound as a colorless oil. Mass spectrum (CI (CH4), m/z) Calcd. for C10H17N3OSi, 224.1 (M+H). found 224.1.
70%	With potassium carbonate; In acetone; at 20℃; for 10h;Product distribution / selectivity;	A flask charged with <strong>[57090-88-7]imidazole-4-carbonitrile</strong> (0.5 g, 5.2 mmol) (Synthesis, 677, 2003), 2-(trimcthylsilyl)cthoxymcthyl chloride (SEMCl) (0.95 mL, 5.3 mmol), K2CO3 (1.40 g, 10.4 mmol), and acetone (5 mL) was stirred for 10 h at RT. The mixture was diluted with EtOAc (20 mL) and washed with water (20 mL) and brine (20 mL) and the organic layer dried over MgSO4. The crude product was eluted from a 20-g SPE cartridge (silica) with 30 percent EtOAc/hexane to give 0.80 g (70 percent) of the title compound as a colorless oil. Mass spectrum (CT (CH4), m/z) Calcd. for C1OHi7NsOSi, 224.1 (M+H), found 224.1.
70%	With potassium carbonate; In acetone; at 20℃; for 10h;	Example 11; 4-Cyano- lH-imidazole-2-carboxylic acid (4-bromo-2-cyclohex- 1 -enyl-phenyl)-amide; a) l-(2-Trimethylsilanyl-ethoxymethyl)-lH-<strong>[57090-88-7]imidazole-4-carbonitrile</strong>; A flask charged with <strong>[57090-88-7]imidazole-4-carbonitrile</strong> (0.50 g, 5.2 mmol) (Synthesis, 677, 2003), <n="43"/>2-(trimethylsilyl)ethoxymethyl chloride (SEMCl) (0.95 mL, 5.3 mmol), K2CO3 (1.40 g, 10.4 mmol), and acetone (5 mL) was stirred for 10 h at RT. The mixture was diluted with EtOAc (20 mL) and washed with water (20 mL) and brine (20 mL) and the organic layer dried over MgSO4. ,The crude product was eluted from a 20-g SPE cartridge (silica) with 30 percent EtOAc/hexane to 'give 0.80 g (70 percent) of the title compound as a colorless oil. Mass spectrum (CI (CH4), m/z) Calcd. for Cj0HnN3OSi, 224.1 (M+H), found 224.1.
	With sodium hydride; In tetrahydrofuran; at 20℃; for 18h;	To a round bottom flask was added NaH (60percent in mineral oil) (200 mg, 5.22 mmol) in dry THF (12 ml), followed by the addtion of <strong>[57090-88-7]1H-<strong>[57090-88-7]imidazole-4-carbonitrile</strong></strong> (400 mg, 4.3 mmol), SEMCl (1433 mg, 8.6 mmol). The reactiom mixture was stirred at room temperature for 18 h. The reaction mixture was concentrated in vacuo. The residue was dissolved in EtO Ac/sat. NaHCO3. The organic phase was separated, washed with water, <n="131"/>brine, dried over anhy. Na2SO4, filtered and concentrated. The resulting residue was purified by flash chromatography on silica gel (0-3percent MeOH/CH2Cl2). The product fractions were collected and concentrated to afford 355 mg of 1-(2-trimethylsilanyl- ethoxymethyl)-<strong>[57090-88-7]1H-<strong>[57090-88-7]imidazole-4-carbonitrile</strong></strong>, m/z 224.6 [M+l]+.

References: [1]Patent: WO2006/47277,2006,A2 .Location in patent: Page/Page column 41-42.
[2]Patent: WO2006/47504,2006,A1 .Location in patent: Page/Page column 36-37.
[3]Patent: US2006/281788,2006,A1 .Location in patent: Page/Page column 47.
[4]Patent: US2007/249649,2007,A1 .Location in patent: Page/Page column 35.
[5]Patent: US2007/249593,2007,A1 .Location in patent: Page/Page column 22-23.
[6]Patent: US2007/249608,2007,A1 .Location in patent: Page/Page column 24.
[7]Patent: US2008/51402,2008,A1 .Location in patent: Page/Page column 33-34.
[8]Patent: WO2007/48088,2007,A2 .Location in patent: Page/Page column 59.
[9]Patent: WO2007/123516,2007,A1 .Location in patent: Page/Page column 40-41.
[10]Patent: WO2009/70485,2009,A1 .Location in patent: Page/Page column 128-129.

19
[ 76513-69-4 ]
[ 57090-88-7 ]
[ 854044-50-1 ]
[ 885693-61-8 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In acetone; at 20℃; for 20h;	A 22-L, four-neck, round-bottom flask equipped with a mechanical stirrer, a temperature probe, and an addition funnel with a nitrogen inlet was charged with IH- <strong>[57090-88-7]imidazole-4-carbonitrile</strong> (830 g, 8.91 mol, as prepared in the previous step), potassium carbonate (2.47 kg, 17.8 mol), and acetone (6.0 L). Agitation was initiated and the mixture was cooled to 10 0C with an ice bath. SEMCl (1.50 kg, 9.00 mol) was added through the addition funnel over 210 min to maintain the internal temperature below 15 0C. The reaction was then allowed to warm to ambient temperature and stirred at ambient temperature overnight (20 h). The reaction mixture was then cooled in an ice bath to 10 0C and quenched by the slow addition of water (8.0 L) over 30 min to maintain the internal temperature below 30 °C. The resulting mixture was transferred to a 22-L separatory funnel and extracted with ethyl acetate (2 x 7.0 L). The combined organics were concentrated under reduced pressure at 35 0C to give the crude product as a dark brown oil, EPO <DP n="133"/>which was purified through a plug of silica gel (16.5 x 20 cm, 2.4 kg silica gel) using 2:1 heptane/ethyl acetate (15 L) as eluent. The fractions containing the product were combined and concentrated under reduced pressure at 35 0C to afford a mixture of the title compounds as a light brown oil [1785 g, 90percent). The 1H NMR spectrum was consistent with the assigned structure and indicated the presence of a 64:36 ratio of regioisomers.
	With potassium carbonate; In acetone; at 10 - 20℃; for 23.5h;Product distribution / selectivity;	b) l-(2-Trimethylsilanyl-ethoxymethyl)-lH-<strong>[57090-88-7]imidazole-4-carbonitrile</strong> and 3-(2- trimethylsilanyl-ethoxymethyl)-3H-<strong>[57090-88-7]imidazole-4-carbonitrile</strong>; A 22-L, four-neck, round-bottom flask equipped with a mechanical stirrer, a temperature probe, and an addition funnel with a nitrogen inlet was charged with IH- <strong>[57090-88-7]imidazole-4-carbonitrile</strong> (830 g, 8.91 mol, as prepared in the previous step), potassium carbonate (2.47 kg, 17.8 mol), and acetone (6.0 L). Agitation was initiated and the mixture was cooled to 10 0C with an ice bath. SEMCl (1.50 kg, 9.00 mol) was added through the addition funnel over 210 min to maintain the internal temperature below 15 °C. The reaction was then allowed to warm to ambient temperature and stirred at ambient temperature overnight (20 h). The reaction mixture was then cooled in an ice bath to 10 °C and quenched by the slow addition of water (8.0 L) over 30 min to maintain the internal temperature below 30 °C. The resulting mixture was transferred to a 22-L separatory funnel and extracted with ethyl acetate (2 x 7.0 L). The combined organics were EPO <DP n="149"/>concentrated under reduced pressure at 35 °C to give the crude product as a dark brown oil, which was purified through a plug of silica gel (16.5 x 20 cm, 2.4 kg silica gel) using 2:1 heptane/ethyl acetate (15 L) as eluent. The fractions containing the product were combined and concentrated under reduced pressure at 35 °C to afford a mixture of the title compounds as a light brown oil [1785 g, 90percent). The 1H NMR spectrum was consistent with the assigned structure and indicated the presence of a 64:36 ratio of regioisomers.
	With potassium carbonate; In acetone; at 0 - 10℃; for 23.5h;	A 22-L, four-neck, round-bottom flask equipped with a mechanical stirrer, a temperature probe, and an addition funnel with a nitrogen inlet was charged with <strong>[57090-88-7]1H-<strong>[57090-88-7]imidazole-4-carbonitrile</strong></strong> (830 g, 8.91 mol, as prepared in the previous step), potassium carbonate (2.47 kg, 17.8 mol), and acetone (6.0 L). Agitation was initiated and the mixture was cooled to 10° C. with an ice bath. SEMCl (1.50 kg, 9.00 mol) was added through the addition funnel over 210 min to maintain the internal temperature below 15° C. The reaction was then allowed to warm to ambient temperature and stirred at ambient temperature overnight (20 h). The reaction mixture was then cooled in an ice bath to 10° C. and quenched by the slow addition of water (8.0 L) over 30 min to maintain the internal temperature below 30° C. The resulting mixture was transferred to a 22-L separatory funnel and extracted with ethyl acetate (2.x.7.0 L). The combined organics were concentrated under reduced pressure at 35° C. to give the crude product as a dark brown oil, which was purified through a plug of silica gel (16.5.x.20 cm, 2.4 kg silica gel) using 2:1 heptane/ethyl acetate (15 L) as eluent. The fractions containing the product were combined and concentrated under reduced pressure at 35° C. to afford a mixture of the title compounds as a light brown oil [1785 g, 90percent). The 1H NMR spectrum was consistent with the assigned structure and indicated the presence of a 64:36 ratio of regioisomers.

	With potassium carbonate; In acetone; at 10 - 20℃; for 20h;	A 22-L, four-neck, round-bottom flask equipped with a mechanical stirrer, a temperature probe, and an addition funnel with a nitrogen inlet was charged with <strong>[57090-88-7]1H-<strong>[57090-88-7]imidazole-4-carbonitrile</strong></strong> (830 g, 8.91 mol, as prepared in the previous step), potassium carbonate (2.47 kg, 17.8 mol), and acetone (6.0 L). Agitation was initiated and the mixture was cooled to 10° C. with an ice bath. SEMCl (1.50 kg, 9.00 mol) was added through the addition funnel over 210 min to maintain the internal temperature below 15° C. The reaction was then allowed to warm to ambient temperature and stirred at ambient temperature overnight (20 h). The reaction mixture was then cooled in an ice bath to 10° C. and quenched by the slow addition of water (8.0 L) over 30 min to maintain the internal temperature below 30° C. The resulting mixture was transferred to a 22-L separatory funnel and extracted with ethyl acetate (2.x.7.0 L). The combined organics were concentrated under reduced pressure at 35° C. to give the crude product as a dark brown oil, which was purified through a plug of silica gel (16.5.x.20 cm, 2.4 kg silica gel) using 2:1 heptane/ethyl acetate (15 L) as eluent. The fractions containing the product were combined and concentrated under reduced pressure at 35° C. to afford a mixture of the title compounds as a light brown oil [1785 g, 90percent). The 1H NMR spectrum was consistent with the assigned structure and indicated the presence of a 64:36 ratio of regioisomers.
	With potassium carbonate; In acetone; at 10 - 30℃; for 23.5h;Product distribution / selectivity;	A 22-L, four-neck, round-bottom flask equipped with a mechanical stirrer, a temperature probe, and an addition funnel with a nitrogen inlet was charged with IH- <strong>[57090-88-7]imidazole-4-carbonitrile</strong> (830 g, 8.91 mol, as prepared in the previous step), potassium carbonate (2.47 kg, 17.8 mol), and acetone (6.0 L). Agitation was initiated and the mixture was cooled to 10 0C with an ice bath. SEMCl (1.50 kg, 9.00 mol) was added through the addition funnel over 210 min to maintain the internal temperature below 15 0C. The reaction was then allowed to warm to ambient temperature and stirred at ambient temperature overnight (20 h). The reaction mixture was then cooled in an ice bath to 10 0C and quenched by the slow addition of water (8.0 L) over 30 min to maintain the internal temperature below 30 0C. The resulting mixture was transferred to a 22-L separatory funnel and extracted with ethyl acetate (2 x 7.0 L). The combined organics were concentrated under reduced pressure at 35 0C to give the crude product as a dark brown oil, which was purified through a plug of silica gel (16.5 x 20 cm, 2.4 kg silica gel) using 2:1 heptane/ethyl acetate (15 L) as eluent. The fractions containing the product were combined and concentrated <n="150"/>under reduced pressure at 35 °C to afford a mixture of the title compounds as a light brown oil [1785 g, 90percent). The 1H NMR spectrum was consistent with the assigned structure and indicated the presence of a 64:36 ratio of regioisomers.
	With potassium carbonate; In acetone; at 20℃; for 48h;Inert atmosphere;	lH-<strong>[57090-88-7]imidazole-4-carbonitrile</strong> (1 g, 10.74 mmol) and potassium carbonate (2.97 g, 21.49 mmol) were added to a round bottomed flask and placed under an atmosphere of nitrogen by evacuation-refill. Acetone (10 mL) was added, evacuation-refill of the vessel repeated, and the mixture stirred prior to addition of (2- (chloromethoxy)ethyl)trimethylsilane (2.091 mL, 11.82 mmol). The reaction vessel was placed under an atmosphere of nitrogen and stirred at RT for 48 h. The solvent was removed under reduced pressure, and the residue redissolved in 30 mL EtOAc and washed sequentially with 20 mL water and 20 mL brine. The combined aqueous layers were extracted with further EtOAc (2 x 30 mL). The organic layers were combined and passed through a hydrophobic frit, and the solvent was removed under reduced pressure. The sample was dissolved in DCM and purified by column chromatography using a silica cartridge (120 g) with an ethyl acetate-cyclohexane solvent system [3CV, 10-20percent; 3CV, 20percent; 5CV, 20-50percent; 9CV, 50percent]. The appropriate fractions were combined and the solvent removed in vacuo to afford the title compound in a 2: 1 ratio of the l-((2-(trimethylsilyl)ethoxy)methyl)-lH-<strong>[57090-88-7]imidazole-4-carbonitrile</strong> and l-((2- (trimethylsilyl)ethoxy)methyl)-lH-imidazole-5-carbonitrile regioisomers, as a pale yellow oil (1.71 g, 7.66 mmol, 71percent). LCMS (System B): tRET = 1.08 min; MH+ 224 (both regioisomers).

References: [1]Patent: WO2006/47277,2006,A2 .Location in patent: Page/Page column 131-132.
[2]Patent: WO2006/47504,2006,A1 .Location in patent: Page/Page column 147-148.
[3]Patent: US2006/281788,2006,A1 .Location in patent: Page/Page column 89.
[4]Patent: US2008/51402,2008,A1 .Location in patent: Page/Page column 75.
[5]Synthesis,2008,p. 3377 - 3379.
[6]Patent: WO2007/48088,2007,A2 .Location in patent: Page/Page column 147-148.
[7]Patent: WO2018/41964,2018,A1 .Location in patent: Page/Page column 53.

20
[ 875155-17-2 ]
[ 57090-88-7 ]
[ 875155-53-6 ]

Yield	Reaction Conditions	Operation in experiment
8.8%	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; for 24h;Heating / reflux;	A solution of 5-fluoro-2-nitro-4-trifluoromethyl-benzoic acid methyl ester (3.2 g, 11.98 mmol), 1 H-<strong>[57090-88-7]imidazole-4-carbonitrile</strong> (2.017g, 14.37 mmol) and ethyl-diisopropyl-amine (8.4 ml, 47.9 mmol) in 10 ml of dioxane is heated to reflux for 24 hours. The solution is allowed to cool to room temperature and evaporated. The residue is chromatographed on silica gel using gradients of dichloromethane and methanol to give 0.36 g (1.05 mmol, 8.8percent) of amorphous 5-(4-cyano-imidazol-1-yl)-2-nitro-4-trifluoromethyl-benzoicacid methyl ester, ES-MS: m/z 341 [M+Hf.

References: [1]Patent: WO2006/10591,2006,A2 .Location in patent: Page/Page column 88.

21
(2R,4R)-1-Allyloxycarbonyl-4-methanesulfonyloxy-2-(2methanesulfonyloxyethyl)pyrrolidine [ No CAS ]
[ 57090-88-7 ]
[ 156442-40-9 ]

Yield	Reaction Conditions	Operation in experiment
		Preparation 30-1) (2R,4R)-1-Allyloxycarbonyl-4-methanesulfonyloxy-2-(2methanesulfonyloxyethyl)pyrrolidine (36.1 g) was reacted with <strong>[57090-88-7]4-cyanoimidazole</strong> (10.0 g) and potassium t-butoxide (12.0 g) in substantially the same manner as Preparation 10-3) to give (2R,4R)-1-allyloxycarbonyl-2-[2-(4-cyanoimidazol-1-yl)ethyl]-4-methanesulfonyloxypyrrolidine (14.1 g) as a yellow paste. NMR (CDCl3, 200 MHz, delta): 1.8-2.0 (2H, m), 2.2-2.6 (2H, m), 3.05 (3H, s), 3.5-3.6 (1H, m), 3.9-4.2 (4H, m), 4.6-4.7 (2H, m), 5.2-5.4 (3H, m), 5.8-6.0 (1H, m), 7.5-7.7 (2H, m)

References: [1]Patent: US5608056,1997,A .

22
[ 3034-50-2 ]
[ 57090-88-7 ]

Yield	Reaction Conditions	Operation in experiment
82%		Example 72An alternate method'for the synthesis of the imidazole intermediate is described below:4-Cyano-l-(2-trimethylsilanyl-ethoxymethyl)-lH-imidazole-2-carboxylic acid potassium salt a) lH-Imidazole-4-carbonitrile; '-NHA 22-L, four-neck, round-bottom flask equipped with a mechanical stirrer, a temperature probe, a condenser, and an addition funnel with a nitrogen inlet was charged with lH-imidazole-4-carboxaldehyde (Aldrich, 1.10 kg, 11.5 mol) and pyridine (3.0 L, 3.0 mol). The reaction flask was cooled to 8 0C with an ice bath and hydroxylamine hydrochloride (871 g, 12.5 mol) was added slowly in portions to maintain the internal temperature below 30 °C. The reaction was allowed to cool to ambient temperature and stirred for 2 h at ambient temperature. The resulting thick yellow solution was heated to 80 0C with a heating mantle and acetic anhydride (2.04 L, 21.6 mol) was added dropwise EPO <DP n="148"/>over 200 min to maintain the temperature below 110 °C during the addition. The reaction mixture was heated at 100 0C for 30 min, after which time it was allowed to cool to ambient temperature and then further cooled in an ice bath. The pH was adjusted to 8.0 (pH meter) by the addition of 25 wt percent NaOH (5.5 L) at such a rate that the internal temperature was maintained below 30 °C. The reaction mixture was then transferred into a 22-L separatory funnel and extracted with ethyl acetate (6.0 L). The combined organic layer was washed with brine (2 x 4.0 L), dried over MgSO4, filtered, and concentrated to dryness under reduced pressure at 35 °C to give the crude product as a yellow semisolid. The resulting semisolid was suspended in toluene (3.0 L) and stirred for 1 h, after which time it was filtered to give a light yellow solid, which was resuspended in toluene (3.0 L) and stirred for 1 h. The resulting slurry was filtered and the filter cake washed with toluene (2 x 500 mL) to give the title compound as a light yellow solid [870 g, 82percent). The 1H and 13C NMR spectra were consistent with the assigned structure.
82%	With pyridine; hydroxylamine hydrochloride; acetic anhydride; at 0 - 110℃; for 5.83333h;	A 22-L, four-neck, round-bottom flask equipped with a mechanical stirrer, a temperature probe, a condenser, and an addition funnel with a nitrogen inlet was charged with 1H-imidazole-4-carboxaldehyde (Aldrich, 1.10 kg, 11.5 mol) and pyridine (3.0 L, 3.0 mol). The reaction flask was cooled to 8° C. with an ice bath and hydroxylamine hydrochloride (871 g, 12.5 mol) was added slowly in portions to maintain the internal temperature below 30° C. The reaction was allowed to cool to ambient temperature and stirred for 2 h at ambient temperature. The resulting thick yellow solution was heated to 80° C. with a heating mantle and acetic anhydride (2.04 L, 21.6 mol) was added dropwise over 200 min to maintain the temperature below 110° C. during the addition. The reaction mixture was heated at 100° C. for 30 min, after which time it was allowed to cool to ambient temperature and then further cooled in an ice bath. The pH was adjusted to 8.0 (pH meter) by the addition of 25 wt percent NaOH (5.5 L) at such a rate that the internal temperature was maintained below 30° C. The reaction mixture was then transferred into a 22-L separatory funnel and extracted with ethyl acetate (6.0 L). The combined organic layer was washed with brine (2.x.4.0 L), dried over MgSO4, filtered, and concentrated to dryness under reduced pressure at 35° C. to give the crude product as a yellow semisolid. The resulting semisolid was suspended in toluene (3.0 L) and stirred for 1 h, after which time it was filtered to give a light yellow solid, which was resuspended in toluene (3.0 L) and stirred for 1 h. The resulting slurry was filtered and the filter cake washed with toluene (2.x.500 mL) to give the title compound as a light yellow solid [870 g, 82percent). The 1H and 13C NMR spectra were consistent with the assigned structure.
82%		a) 1H-Imidazole-4-carbonitrile A 22-L, four-neck, round-bottom flask equipped with a mechanical stirrer, a temperature probe, a condenser, and an addition funnel with a nitrogen inlet was charged with 1H-imidazole-4-carboxaldehyde (Aldrich, 1.10 kg, 11.5 mol) and pyridine (3.0 L, 3.0 mol). The reaction flask was cooled to 8° C. with an ice bath and hydroxylamine hydrochloride (871 g, 12.5 mol) was added slowly in portions to maintain the internal temperature below 30° C. The reaction was allowed to cool to ambient temperature and stirred for 2 h at ambient temperature. The resulting thick yellow solution was heated to 80° C. with a heating mantle and acetic anhydride (2.04 L, 21.6 mol) was added dropwise over 200 min to maintain the temperature below 110° C. during the addition. The reaction mixture was heated at 100° C. for 30 min, after which time it was allowed to cool to ambient temperature and then further cooled in an ice bath. The pH was adjusted to 8.0 (pH meter) by the addition of 25 wt percent NaOH (5.5 L) at such a rate that the internal temperature was maintained below 30° C. The reaction mixture was then transferred into a 22-L separatory funnel and extracted with ethyl acetate (6.0 L). The combined organic layer was washed with brine (24.0 L), dried over MgSO4, filtered, and concentrated to dryness under reduced pressure at 35° C. to give the crude product as a yellow semisolid. The resulting semisolid was suspended in toluene (3.0 L) and stirred for 1 h, after which time it was filtered to give a light yellow solid, which was resuspended in toluene (3.0 L) and stirred for 1 h. The resulting slurry was filtered and the filter cake washed with toluene (2500 mL) to give the title compound as a light yellow solid [870 g, 82percent). The 1H and 13C NMR spectra were consistent with the assigned structure.

82%

A 22-L, four-neck, round-bottom flask equipped with a mechanical stirrer, a temperature probe, a condenser, and an addition funnel with a nitrogen inlet was charged with lH-imidazole-4-carboxaldehyde (Aldrich, 1.10 kg, 11.5 mol) and pyridine (3.0 L, 3.0 mol). The reaction flask was cooled to 8 0C with an ice bath and hydroxylamine hydrochloride (871 g, 12.5 mol) was added slowly in portions to maintain the internal temperature below 30 0C. The reaction was allowed to cool to ambient temperature and stirred for 2 h at ambient temperature. The resulting thick yellow solution was heated to 80 0C with a heating mantle and acetic anhydride (2.04 L5 21.6 mol) was added dropwise over 200 min to maintain the temperature below 110 0C during the addition. The reaction mixture was heated at 100 0C for 30 min, after which time it was allowed to cool to ambient temperature and then further <n="149"/>cooled in an ice bath. The pH was adjusted to 8.0 (pH meter) by the addition of 25 wt percent NaOH (5.5 L) at such a rate that the internal temperature was maintained below 30 °C. The reaction mixture was then transferred into a 22-L separatory funnel and extracted with ethyl acetate (6.0 L). The combined organic layer was washed with brine (2 x 4.0 L), dried over MgSO4, filtered, and concentrated to dryness under reduced pressure at 35 0C to give the crude product as a yellow semisolid. The resulting semisolid was suspended in toluene (3.0 L) and stirred for 1 h, after which time it was filtered to give a light yellow solid, which was resuspended in toluene (3.0 L) and stirred for 1 h. The resulting slurry was filtered and the filter cake washed with toluene (2 x 500 nxL) to give the title compound as a light yellow solid [870 g, 82percent). The 1H and 13C NMR spectra were consistent with the assigned structure.

References: [1]Patent: WO2006/47504,2006,A1 .Location in patent: Page/Page column 146-147.
[2]Patent: US2006/281788,2006,A1 .Location in patent: Page/Page column 88-89.
[3]Patent: US2008/51402,2008,A1 .Location in patent: Page/Page column 74-75.
[4]Patent: WO2007/48088,2007,A2 .Location in patent: Page/Page column 146-147.
[5]Synthesis,2008,p. 3377 - 3379.

23
[ 57090-88-7 ]
4-Imidazolylthioformimidate dihydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In diethyl ether; ethanethiol;	4. 4-Imidazolylthioformimidate dihydrochloride To 900 mg. of <strong>[57090-88-7]4-cyanoimidazole</strong> in 30 ml. of ethyl mercaptan cooled to 0° C. in a glass pressure bottle is added over 15 min. sufficient hydrogen chloride gas to saturate the solution. The sealed bottle is allowed to remain at room temperature for 20 min., and its contents then treated with 100 ml. of diethyl ether and filtered to give 1.7 g. of the product, m.p. 155°-158° C., dec.

References: [1]Patent: US4025506,1977,A .

24
[ 108-20-3 ]
[ 920-39-8 ]
[ 57090-88-7 ]
[ 247174-71-6 ]

Yield	Reaction Conditions	Operation in experiment
82%	With sodium hydroxide; sulfuric acid; In tetrahydrofuran; water;	Example 1 Production of 1-(1H-imidazol-4-yl)-2-methyl-1-propanone A solution of <strong>[57090-88-7]4-cyanoimidazole</strong> (42.7 g, 0.458 mol) in THF (500 ml) was added dropwise over 30 min to a solution (1.4 L, 1.47 mol, 3.2 equivalents) of 1.1 M isopropyl magnesium bromide in THF at 0 to 10°C under a nitrogen atmosphere. The mixture was stirred at 15 to 25°C for 3 h. Water (430 ml) and 10percent aqueous sulfuric acid solution (860 ml) were successively added dropwise, and the mixture was stirred at 30 min. A 30percent aqueous sodium hydroxide solution was added dropwise to adjust the pH to 8. After partitioning, the aqueous layer was extracted with ethyl acetate (300 ml * 2). The organic layer was combined, and the mixture was washed successively with saturated aqueous sodium hydrogencarbonate and saturated brine, and concentrated under reduced pressure. The concentration residue was broken up with isopropyl ether (300 ml). The crystals were collected by filtration and washed with isopropyl ether. The crystals were dried in vacuo (40°C) to give 1-(1H-imidazol-4-yl)-2-methyl-1-propanone (51.9 g, yield 82percent). 1H-NMR (CDCl3): delta1.25(6H, d, J=6.9Hz), 3.36(1H, quint, J=6.9Hz), 7.81(1H, s), 7.87(1H, s)

References: [1]Patent: EP1193258,2002,A1 .

25
nickel(II) cyanide [ No CAS ]
tetra-n-butylammonium hydroxide [ No CAS ]
[ 57090-88-7 ]
(NBu₄)4[Ni(4-cyanoimidazolate)6]*2H₂O [ No CAS ]

References: [1]Inorganic Chemistry,2004,vol. 43,p. 4897 - 4902.

26
[ 76513-69-4 ]
[ 57090-88-7 ]
[ 854044-51-2 ]

Yield	Reaction Conditions	Operation in experiment
1.24 g		lH-<strong>[57090-88-7]imidazole-4-carbonitrile</strong> (1 g, 10.74 mmol) and potassium carbonate (2.97 g, 21.49 mmol) were added to a round bottomed flask and placed under an atmosphere of nitrogen by evacuation-refill. Acetone (10 mL) was added, evacuation-refill of the vessel repeated, and the mixture stirred prior to addition of (2- (chloromethoxy)ethyl)trimethylsilane (2.091 mL, 11.82 mmol). The reaction vessel was placed under an atmosphere of nitrogen and stirred at RT for 48 h. The solvent was removed under reduced pressure, and the residue redissolved in 30 mL EtOAc and washed sequentially with 20 mL water and 20 mL brine. The combined aqueous layers were extracted with further EtOAc (2 x 30 mL). The organic layers were combined and passed through a hydrophobic frit, and the solvent was removed under reduced pressure. The sample was dissolved in DCM and purified by column chromatography using a silica cartridge (120 g) with an ethyl acetate-cyclohexane solvent system [3CV, 10-20percent; 3CV, 20percent; 5CV, 20-50percent; 9CV, 50percent]. The appropriate fractions were combined and the solvent removed in vacuo to afford the title compound in a 2: 1 ratio of the l-((2-(trimethylsilyl)ethoxy)methyl)-lH-<strong>[57090-88-7]imidazole-4-carbonitrile</strong> and l-((2- (trimethylsilyl)ethoxy)methyl)-lH-imidazole-5-carbonitrile regioisomers, as a pale yellow oil (1.71 g, 7.66 mmol, 71percent). LCMS (System B): tRET = 1.08 min; MH+ 224 (both regioisomers). l-((2-(Trimethylsilyl)ethoxy)methyl)-lH-<strong>[57090-88-7]imidazole-4-carbonitrile</strong> (for an example preparation, see Intermediate 15, 1.68 g, 7.52 mmol (2: 1 ratio of l-((2- (trimethylsilyl)ethoxy)methyl)-lH-<strong>[57090-88-7]imidazole-4-carbonitrile</strong> and H(2- (trimethylsilyl)ethoxy)methyl)-lH-imidazole-5-carbonitrile)) was added to a round bottomed flask containing THF (40 mL). Once dissolved, /V-bromosuccinimide (1.473 g, 8.27 mmol) was added, and the flask placed under an atmosphere of nitrogen. The reaction mixture was stirred at 60 °C overnight. Further 0.2 equivalents of /V-bromosuccinimide (0.268 g, 1.504 mmol) was added to the reaction mixture and the reaction left stirring at 60 °C for a further 8h. The reaction mixture was quenched with saturated sodium hydrogencarbonate solution (40 mL) and brine (40 mL) and extracted with EtOAc (3 x 40 mL). The combined organic layers were passed through a hydrophobic frit and the solvent removed under reduced pressure. The sample was loaded as a neat liquid and purified by column chromatography using a silica cartridge (80 g) with an ethyl acetate-cyclohexane solvent system [3CV, 0percent; 7CV, 0-10percent; 3CV, 10percent]. The appropriate fractions were combined and the solvent removed in vacuo to give the crude product. The crude product was dissolved in diethyl ether and filtered through Celite®, the solvent was removed from the filtrate under reduced pressure to afford the title compound as a pale yellow oil, (1.24 g, 4.10 mmol, 55percent). LCMS (System A): tRET = 1.23 min; MH+ 302, 304.

References: [1]Synthesis,2008,p. 3377 - 3379.
[2]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 3632 - 3637.
[3]Patent: WO2018/41964,2018,A1 .Location in patent: Page/Page column 53.

27
[ 57090-88-7 ]
[ 75-26-3 ]
[ 76-05-1 ]
[ 1159733-97-7 ]
[ 1159734-00-5 ]

Yield	Reaction Conditions	Operation in experiment
		To a round bottom flask was added <strong>[57090-88-7]1H-<strong>[57090-88-7]imidazole-4-carbonitrile</strong></strong> (300 mg, 3.22 mmol), 2- bromopropane (794 mg, 6.44 mmol), and K2CO3 (890 mg, 6.44 mmol) in DMF (9 ml). The reactiom mixture was stirred at room temperature for 18 h. The reaction mixture was filtered. The solvent was concentrated in vacuo. The residue was purified by prepHPLC to afford 310 mg of 1-Isopropyl-lH-<strong>[57090-88-7]imidazole-4-carbonitrile</strong> TFA salt and 71 mg of 3- isopropyl-3H-<strong>[57090-88-7]imidazole-4-carbonitrile</strong> TFA salt region-isomer.1-Isopropyl-lH-irnidazole-4-carboriitrile TFA salt was dissolved in EtOAc, washed with sat. NaHCO3, brine, dried under anhy. Na2SO4, filtered and concentrated to afford 200 mg of 1-isopropyl-l/Mrnidazole-4-carbonitrile as a colorless oil, m/z 136.5 [M+l]+.

References: [1]Patent: WO2009/70485,2009,A1 .Location in patent: Page/Page column 128.

28
[ 527-73-1 ]
zinc nitrate tetrahydrate [ No CAS ]
[ 68-12-2 ]
[ 57090-88-7 ]
[ 1136998-75-8 ]

References: [1]Journal of the American Chemical Society,2009,vol. 131,p. 3875 - 3877.

29
[ 105-36-2 ]
[ 57090-88-7 ]
[ 1154030-58-6 ]

Yield	Reaction Conditions	Operation in experiment
60%	With sodium ethanolate; In ethanol; at 20℃; for 16h;	3.3 g (35.3 mmol) <strong>[57090-88-7]1H-<strong>[57090-88-7]imidazole-4-carbonitrile</strong></strong> [Matthews et al., J. Org. Chem. 1986, 51, 3228-3231] are initially introduced into 13.2 ml (11.5 g, 35.3 mmol) 21percent strength sodium ethylate solution in ethanol and 4.3 ml (6.5 g, 38.9 mmol) ethyl bromoacetate are added. The reaction mixture is stirred at RT for 16 h. For working up, the solid which has precipitated out is filtered off, the residue on the filter is washed with ethanol and the filtrate is concentrated in vacuo. Diisopropyl ether is added to the residue, the mixture is filtered again, the filtrate is concentrated again on a rotary evaporator and the residue is dried in vacuo.Yield: 3.8 g (60percent of th.)LC-MS (Method 1): Rt=1.17 min; MS (ESIpos): m/z=180 [M+H]+;1H-NMR (400 MHz, DMSO-d6): delta=8.12 (s, 1H), 7.88 (s, 1H), 5.06 (s, 2H), 4.18 (q, 2H), 1.22 (t, 3H).
	In ethanol; sodium ethanolate;	Example 1A Ethyl (4-cyano-1H-imidazol-1-yl)acetate 3.3 g (35.3 mmol) of <strong>[57090-88-7]1H-<strong>[57090-88-7]imidazole-4-carbonitrile</strong></strong> [Matthews et al., J. Org. Chem. 1986, 51, 3228-3231] are initially charged in 13.2 ml (11.5 g, 35.3 mmol) of 21percent strength sodium ethoxide solution in ethanol, and 4.3 ml (6.5 g, 38.9 mmol) of ethyl bromoacetate are added. The reaction mixture is stirred at RT for 16 h. For work-up, the precipitated solid is filtered off, the filter residue is washed with ethanol and the filtrate is concentrated under reduced pressure. Diisopropyl ether is added to the residue, the mixture is filtered again, the filtrate is once more concentrated on a rotary evaporator and the residue is dried under reduced pressure. Yield: 3.8 g (60percent of theory) LC-MS (Method 1): Rt=1.17 min; MS (ESIpos): m/z=180 [M+H]+; 1H-NMR (400 MHz, DMSO-d6): delta=8.12 (s, 1H), 7.88 (s, 1H), 5.06 (s, 2H), 4.18 (q, 2H), 1.22 (t, 3H).

References: [1]Patent: US2010/305085,2010,A1 .Location in patent: Page/Page column 24.
[2]Patent: US2009/269420,2009,A1 .

30
[ 26832-08-6 ]
[ 57090-88-7 ]

Yield	Reaction Conditions	Operation in experiment
65.9%		In a dried 125 mL, three-neck flask fitted with a magnetic stirrer, temperature probe, a reflux condenser, and a positive nitrogen atmosphere set-up was charged with 4-imidazole carboxamide 2.0 gm (18 mmol), acetonitrile 25 ml, and POCl3 6.6 gm (43.2 mmol). The brown slurry was agitated and heated to reflux. The reaction mixture was maintained at reflux for at least 15 hrs. Then the excess POCl3 was distilled under reduced pressure. After aqueous work up, the reaction mixture was adjusted to a pH of 9-11 using 25percent sodium hydroxide, and extracted with 4.x.70 ml ethyl acetate. The combine ethyl acetate extracts were treated with 20 gm silica gel, distilled under pressure to remove ethyl acetate and to afford 4-cyanoimidazole as a white solid. After drying the 4-cyanoimidazole weighed 1.1 gm (65.9percent yield): HPLC purity, >99.0 area percent; 1H NMR (300 MHz, DMSO-D6) delta 7.89 (s, 1H), 8.08 (s, 1H); 13C NMR (300 MHz, DMSO-D6) delta 111.8, 116.0, 127, 138.1.

References: [1]Patent: US2009/292122,2009,A1 .Location in patent: Page/Page column 12.

31
[ 454-16-0 ]
[ 57090-88-7 ]
[ 1263868-22-9 ]

Yield	Reaction Conditions	Operation in experiment
89%	With potassium carbonate; In N,N-dimethyl-formamide; at 120℃;	To a solution of lH-Imidazole-4-carbonitrile (300 mg, 3.22 mmol) and 4-Fluoro- 3-methoxynitrobenzene (552 mg, 3.22 mmol) in DMF (Volume: 6446 mul) was added K2CO3 (891 mg, 6.45 mmol). The resulting mixture was brought to 120 0C and stirred overnight. The reaction mixture was diluted with EtOAc (20 mL), washed with water (2 x 10 mL), brine (10 mL), dried over MgSO4, filtered and concentrated in vacuo to give 1- (2-methoxy-4-nitrophenyl)-lH-<strong>[57090-88-7]imidazole-4-carbonitrile</strong> (698 mg, 2.86 mmol, 89 percent yield). LC-MS (M+H)+ = 245.0. IH NMR (500 MHz, MeOD) delta ppm 8.30 - 8.34 (1 H), 8.19 - 8.23 (1 H), 8.09 - 8.12 (1 H), 8.00 - 8.05 (1 H), 7.71 - 7.79 (1 H), 4.02 - 4.10 (3 H).

References: [1]Patent: WO2011/14535,2011,A1 .Location in patent: Page/Page column 38-39.

32
potassiumhexacyanoferrate(II) trihydrate [ No CAS ]
[ 2302-25-2 ]
[ 57090-88-7 ]

References: [1]Angewandte Chemie - International Edition,2013,vol. 52,p. 10035 - 10039.
Angew. Chem.,2013,vol. 125,p. 10219 - 10223.

33
[ 920-39-8 ]
[ 57090-88-7 ]
[ 247174-71-6 ]

References: [1]Organic Process Research and Development,2007,vol. 11,p. 206 - 209.

34
[ 1527467-99-7 ]
[ 57090-88-7 ]
[ 1527467-98-6 ]

Yield	Reaction Conditions	Operation in experiment
39.38%	With copper(I) oxide; iron(III)-acetylacetonate; caesium carbonate; In N,N-dimethyl-formamide; at 90℃; for 20h;	The mixture of 2-[5-(2-Fluoro-phenyl)-3-methyl-3H-[1 ,2,3]triazol-4- ylmethoxy]-5-iodo-pyridine (0.5 g, 1 .22 mmol), 1 H-<strong>[57090-88-7]imidazole-4-carbonitrile</strong> (0.170 g, 1 .82 mmol), cesium carbonate (0.79 g, 2.43 mmol), copper(l)oxide (0.017 g,0.122 mmol), ferric acetylacetonate (0.129 g, 0.365 mmol) in DMF (10 ml) was heated at 90°C for 20 h. The reaction was monitored by TLC and UPLC. The reaction mixture was concentrated under reduced pressure, water was added and extracted with ethylacetate (3 X 50 ml). The organic layer was washed with brine (15 ml), dried over Na2SO and concentrated under reduced pressure to afford crude mass (500 mg, 109percent mass balance). It was purified in grace column using 2percent methanol in chloroform as an eluent to furnish desired 1 -{6-[5-(2-Fluoro- phenyl)-3-methyl-3H-[1 ,2,3]triazol-4-ylmethoxy]-pyridin-3-yl}-1 H-imidazole-4- carbonitrile (0.180 g, 39.38percent) as off-white solid.1H NMR (400 MHz, DMSO-D6): delta 8.68 (d, J = 1 .16 Hz, 1 H), 8.46 (d, J = 2.8 Hz, 1 H), 8.42 (d, J = 1 .12 Hz, 1 H), 8.06 (dd, J = 8.88 & 2.8 Hz, 1 H), 7.61 (dt, J = 7.4 & 1 .6 Hz, 1 H), 7.52-7.48 (m, 1 H), 7.35 (q, J = 9.2 Hz, 2H), 7.05 (d, J = 8.84 Hz, 1 H), 5.53 (s, 2H), 4.18 (s, 3H). UPLC (m/z): 375/377(MH+); HPLC purity: 96.96percent; MP: 178.0-181 .5°C

References: [1]Patent: WO2014/1281,2014,A1 .Location in patent: Page/Page column 17; 18.

35
[ 75711-00-1 ]
[ 57090-88-7 ]
1-(3-methoxy-5-nitropyridin-2-yl)-1H-imidazole-4-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With potassium carbonate; In dimethyl sulfoxide; at 20 - 50℃; for 16h;Inert atmosphere;	To a stirred solution of 2-chloro-3-methoxy-5-nitropyridine (1.5 g, 79.78 mmol) in DMSO (15 mL) under an argon atmosphere were added potassium carbonate (4.4 g, 31.91 mmol) and <strong>[57090-88-7]1H-<strong>[57090-88-7]imidazole-4-carbonitrile</strong></strong> (890 mg, 9.57 mmol) at room temperature. The reaction mixture was stirred at 50 oC for 16 h. After consumption of the starting material (monitored by TLC), the reaction mixture was diluted with water (20 mL). The obtained solid was filtered and dried in vacuo to obtain 1-(3-methoxy-5-nitropyridin-2-yl)-1H-imidazole-4- carbonitrile (1.1 g, 56percent) as a yellow solid. 1H-NMR (DMSO-d6, 400 MHz): delta 8.97 (s, 1H), 8.86 (s, 1H), 8.67 (s, 1H), 8.47 (s, 1H), 4.11 (s, 3H); LCMS: 245.8 (M+1); (column; X-Select CSH C-18 (50 × 3.0 mm, 3.5 mum); RT 2.96 min. 0.05percent aq TFA: ACN; 0.80 mL/min); TLC: 40percent EtOAc:hexane (Rf: 0.4).
56%	With potassium carbonate; In dimethyl sulfoxide; at 50℃; for 16h;Inert atmosphere;	Synthesis of 1-(3-methoxy-5-nitropyridin-2-yl)-<strong>[57090-88-7]1H-<strong>[57090-88-7]imidazole-4-carbonitrile</strong></strong> To a stirred solution of 2-chloro-3-methoxy-5-nitropyridine (1.5 g, 79.78 mmol) in DMSO (15 mL) under an argon atmosphere were added potassium carbonate (4.4 g, 31.91 mmol) and <strong>[57090-88-7]1H-<strong>[57090-88-7]imidazole-4-carbonitrile</strong></strong> (890 mg, 9.57 mmol) at room temperature. The reaction mixture was stirred at 50° C. for 16 h. After consumption of the starting material (monitored by TLC), the reaction mixture was diluted with water (20 mL). The obtained solid was filtered and dried in vacuo to obtain 1-(3-methoxy-5-nitropyridin-2-yl)-<strong>[57090-88-7]1H-<strong>[57090-88-7]imidazole-4-carbonitrile</strong></strong> (1.1 g, 56percent) as a yellow solid. 1H-NMR (DMSO-d6, 400 MHz): delta 8.97 (s, 1H), 8.86 (s, 1H), 8.67 (s, 1H), 8.47 (s, 1H), 4.11 (s, 3H); LCMS: 245.8 (M+1); (column; X-Select CSH C-18 (50*3.0 mm, 3.5 m); RT 2.96 min. 0.05percent aq TFA: ACN; 0.80 mL/min); TLC: 40percent EtOAc:hexane (Rf: 0.4).

References: [1]Patent: WO2015/109109,2015,A1 .Location in patent: Paragraph 0720.
[2]Patent: US2017/44182,2017,A1 .Location in patent: Paragraph 0997.

36
[ 57090-88-7 ]
[ 74-88-4 ]
[ 66121-66-2 ]

References: [1]Organic Letters,2016,vol. 18,p. 16 - 19.

37
[ 57090-88-7 ]
N-(diphenylmethylene)-2,2,2-trifluoro-1-ethanamine [ No CAS ]
C₁₉H₁₃FN₄ [ No CAS ]

References: [1]RSC Advances,2016,vol. 6,p. 73683 - 73691.

38
[ 57090-88-7 ]
tert-butyl 2-(3-(((1H-imidazol-4-yl)methyl)amino)propanamido)-3-(benzo[d]thiazol-2-yl)-4,7-dihydrothieno[2,3-c]pyridine-6(5H)-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium hydroxide; hydrogen; In methanol; at 20℃; for 15h;	To a stirred solution of compound 4 (0.4 g, 4.29 mmol) in methanol (5 mL), Raney Ni (0.4 g) and aq. NH3 (0.5 mL) was added and stirred under hydrogen atmosphere (balloon pressure) at room temperature for 15 h. Progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was filtered through a pad of celite and the filtrate was evaporated under reduced pressure to afford title compound 2 as yellow coloured thick oil (0.5 g, crude).

References: [1]Patent: WO2016/197078,2016,A1 .Location in patent: Paragraph 753-754.

39
[ 143329-58-2 ]
[ 57090-88-7 ]
1-[1,2,4]triazolo[1,5-a]pyridin-5-yl}-1H-imidazole-4-carbonitrile [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 5663 - 5672.

40
[ 57090-88-7 ]
[ 50-89-5 ]
1-(2-deoxy-β-D-ribofuranosyl)-1H-imidazole-4-carbonitrile [ No CAS ]
1-(2-deoxy-β-D-ribofuranosyl)-1H-imidazole-5-carbonitrile [ No CAS ]

References: [1]Organic and Biomolecular Chemistry,2017,vol. 15,p. 8193 - 8203.

41
2-(1-chloro-cycloprop-1-yl)-2-(2'-chloro-benzyl)-oxirane [ No CAS ]
[ 57090-88-7 ]
1-[2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl]-1H-imidazole-5-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
6%	In N,N-dimethyl-formamide; acetonitrile; at 160℃; for 1.5h;Microwave irradiation;	A solution of <strong>[57090-88-7]4-cyano-1H-imidazole</strong> (500 mg, 1.0 eq, 5.37mmol) and 2-(2-chlorobenzyl)-2-(1- chlorocyclopropyl)oxirane (1.96 g, 1.5 eq, 8.05 mmol) in a mixture of acetonitrile (3 mL) and DMF (1 mL) was heated up to 160°C by microwave irradiation for 90mm. Thereafter the reaction mixture was diluted with dichloromethane, the organic layer washed with sat. aq. NaHCO3 and dried (Mg504), then concentrated to dryness in vacuo. Purification of the residue by flash chromatography [over silica gel, eluted with a mixture ofn-heptane/ethyl acetate (100:0 to 50:50)] followed by preparative HPLC afforded, after evaporation of the solvents, afforded 112 mg (6percent) 1 -[2-( 1 -chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl] - 1H- imidazole-5-carbonitrile (1-06) as a colourless oil.MS (ESI): 336.1 ([M+H]j

References: [1]Patent: WO2018/50456,2018,A1 .Location in patent: Page/Page column 112.

Historical Records

Technical Information

• Blaise Reaction • Catalytic Hydrogenation • Complex Metal Hydride Reductions • Hydride Reductions • Preparation of Aldehydes and Ketones • Preparation of Amines • Ritter Reaction • Thorpe-Ziegler Reaction

Related Functional Groups of
[ 57090-88-7 ]

Nitriles

A254448 [5098-11-3]

5-Amino-1H-imidazole-4-carbonitrile

Similarity: 0.86

A268489 [133123-67-8]

1-Ethyl-1H-imidazole-4,5-dicarbonitrile

Similarity: 0.77

A565667 [50847-09-1]

2-Bromo-1H-imidazole-4,5-dicarbonitrile

Similarity: 0.69

A231804 [70631-95-7]

4-Methyl-1H-imidazole-2-carbonitrile

Similarity: 0.67

A175484 [59489-39-3]

2-Amino-6-cyanopyrazine

Similarity: 0.58

Related Parent Nucleus of
[ 57090-88-7 ]

Imidazoles

A254448 [5098-11-3]

5-Amino-1H-imidazole-4-carbonitrile

Similarity: 0.86

A508676 [822-36-6]

4-Methyl-1H-imidazole

Similarity: 0.81

A268489 [133123-67-8]

1-Ethyl-1H-imidazole-4,5-dicarbonitrile

Similarity: 0.77

A131658 [53316-51-1]

4,5-Dimethyl-1H-imidazole hydrochloride

Similarity: 0.70

A241837 [66247-84-5]

(1H-Imidazol-4-yl)methanamine hydrochloride

Similarity: 0.70

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P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

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CAS No.: 57090-88-7

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CAS No.: 57090-88-7

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[ 57090-88-7 ] Synthesis Path-Downstream 1~41

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[ 57090-88-7 ]

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{[proInfo.proName]}

CAS No.: 57090-88-7

{[proInfo.proName]}

CAS No.: 57090-88-7

Alternative Products

Product Details of [ 57090-88-7 ]

Safety of [ 57090-88-7 ]

Computational Chemistry of [ 57090-88-7 ] Show Less

Physicochemical Properties

Lipophilicity

Water Solubility

Pharmacokinetics

Druglikeness

Medicinal Chemistry

Application In Synthesis of [ 57090-88-7 ]

[ 57090-88-7 ] Synthesis Path-Downstream 1~41

Related Products

Historical Records

Technical Information

Categories

Related Functional Groups of [ 57090-88-7 ]

Nitriles

Related Parent Nucleus of [ 57090-88-7 ]

Imidazoles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Molarity Calculator

Total Compounds Calculator

Dissolution Calculator

Related Functional Groups of
[ 57090-88-7 ]

Related Parent Nucleus of
[ 57090-88-7 ]