[ CAS No. 96797-15-8 ] {[proInfo.proName]}

Name: 96797-15-8|4-Iodo-1-trityl-1H-imidazole|97%
Brand: Ambeed
SKU: A213135
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Quality Control of [ 96797-15-8 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 96797-15-8 ]

SDS Specification

Alternatived Products of [ 96797-15-8 ]

Product Details of [ 96797-15-8 ]

CAS No. :	96797-15-8	MDL No. :	MFCD02179542
Formula :	C₂₂H₁₇IN₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	DXJZJYPLPZEYBH-UHFFFAOYSA-N
M.W :	436.29	Pubchem ID :	618252
Synonyms :

Calculated chemistry of [ 96797-15-8 ]

Physicochemical Properties

Num. heavy atoms :	25
Num. arom. heavy atoms :	23
Fraction Csp3 :	0.05
Num. rotatable bonds :	4
Num. H-bond acceptors :	1.0
Num. H-bond donors :	0.0
Molar Refractivity :	109.55
TPSA :	17.82 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	Yes
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	Yes
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-5.08 cm/s

Lipophilicity

Log Po/w (iLOGP) :	3.45
Log Po/w (XLOGP3) :	5.47
Log Po/w (WLOGP) :	5.33
Log Po/w (MLOGP) :	4.59
Log Po/w (SILICOS-IT) :	5.3
Consensus Log Po/w :	4.83

Druglikeness

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

Water Solubility

Log S (ESOL) :	-6.41
Solubility :	0.000171 mg/ml ; 0.000000391 mol/l
Class :	Poorly soluble
Log S (Ali) :	-5.6
Solubility :	0.00109 mg/ml ; 0.0000025 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-8.85
Solubility :	0.000000621 mg/ml ; 0.0000000014 mol/l
Class :	Poorly soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	3.14

Safety of [ 96797-15-8 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 96797-15-8 ]

* 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 [ 96797-15-8 ]
Downstream synthetic route of [ 96797-15-8 ]

[ 96797-15-8 ] Synthesis Path-Upstream 1~10

1
[ 1252858-34-6 ]
[ 96797-15-8 ]
[ 15469-97-3 ]

Reference： [1] Journal of Medicinal Chemistry, 2011, vol. 54, # 15, p. 5498 - 5507

2
[ 96797-15-8 ]
[ 68-12-2 ]
[ 15469-97-3 ]
[ 67478-50-6 ]
[ 33016-47-6 ]

Reference： [1] Journal of Heterocyclic Chemistry, 1985, vol. 22, p. 57 - 59
[2] Journal of Heterocyclic Chemistry, 1985, vol. 22, p. 57 - 59

3
[ 96797-15-8 ]
[ 68-12-2 ]
[ 33016-47-6 ]

Yield	Reaction Conditions	Operation in experiment
73.2%	Stage #1: With isopropylmagnesium chloride In dichloromethane at 10 - 20℃; Stage #2: at -5 - 20℃; for 10.5 h; Stage #3: With water; ammonium chloride In dichloromethane at 20℃;	Example 1 Preparation of 1-trityl-1 H-imidazole-4-carboxaldehyde1-Trityl-4-iodoimidazole (87, 3g, 0,200mol) was added to stirred methylene chloride (525ml_) in a 4-neck round bottom flask fitted with a mechanical stirrer, a thermometer, a dropping funnel and a tube for argon introduction into the reaction mixture. The reaction mixture was cooled to 1O⁰C, at which point isopropylmagnesium chloride solution in tetrahydrofuran (112ml_, 0,213 mol) was added dropwise <n="7"/>under an argon atmosphere. After addition of isopropylmagnesium chloride the reaction mixture was warmed to 2O⁰C.N,N-Dimethylformamide (47ml_, 0,608mol) was added to methylene chloride (30OmL) in a 4-neck round bottom flask fitted with a mechanical stirrer, a thermometer, a dropping funnel and a tube for argon introduction into the reaction mixture. The reaction mixture was stirred and cooled to (-5) ⁰C and solution of the imidazole Grignard derivative, which was prepared above, was added to the reaction mixture. The reaction mixture was stirred at (-5) ⁰C for half an hour and then at 2O⁰C for 10 hours, at which point 10percent aqueous ammonium chloride solution (30OmL) was added to the reaction mixture.The aqueous layer was extracted with methylene chloride (55OmL). The organic layer was separated and washed with saturated sodium chloride solution, and then the organic layer was stirred with anhydrous magnesium sulphate for 2 hours. The precipitate of magnesium sulphate was separated by filtration. The solvent was removed by distillation at a reduced pressure. Ethanol (20OmL) was added to the distillation residue and the reaction mixture was cooled to (-5)°C for 2 hours.The precipitates were separated by filtration. The obtained intermediate 1-trityl- 1 H-imidazole-4-carboxaldehyde was dried at under reduced pressure. The yield was 56.6g (73.2percent).

Reference： [1] Bioorganic and Medicinal Chemistry, 2003, vol. 11, # 7, p. 1197 - 1205
[2] Farmaco, 2003, vol. 58, # 3, p. 279 - 283
[3] Patent: WO2009/71584, 2009, A1, . Location in patent: Page/Page column 4; 5-6

4
[ 2591-86-8 ]
[ 96797-15-8 ]
[ 33016-47-6 ]

Reference： [1] Organic Preparations and Procedures International, 1996, vol. 28, # 6, p. 709 - 710

5
[ 96797-15-8 ]
[ 68-12-2 ]
[ 15469-97-3 ]
[ 67478-50-6 ]
[ 33016-47-6 ]

Reference： [1] Journal of Heterocyclic Chemistry, 1985, vol. 22, p. 57 - 59
[2] Journal of Heterocyclic Chemistry, 1985, vol. 22, p. 57 - 59

6
[ 96797-15-8 ]
[ 68-12-2 ]
[ 96797-16-9 ]
[ 67478-50-6 ]
[ 33016-47-6 ]

Reference： [1] Journal of Heterocyclic Chemistry, 1985, vol. 22, p. 57 - 59
[2] Journal of Heterocyclic Chemistry, 1985, vol. 22, p. 57 - 59

7
[ 71759-89-2 ]
[ 76-83-5 ]
[ 96797-15-8 ]

Yield	Reaction Conditions	Operation in experiment
94%	With triethylamine In N,N-dimethyl-formamide at 20℃; for 24 h;	To a solution of 3 (3.5 g,18.0 mmol) in DMF (70 mL) was added TEA (3.0 mL, 21.7 mmol) andtrityl chloride (5.5 g, 19.7 mmol). After stirring at 20 C for 24 h, thesolution was poured into water. The solid was filtered to yield thecrude compound that was purified by flash column chromatographyon silica gel to afford 4 as a white solid (7.4 g, 94.0percent). Mp148e150 C. 1H NMR (300 MHz, Chloroform-d) d(ppm) 6.9 (m, 1H),7.0e7.2 (m, 6H), 7.25e7.4 (m, 10H). MS (EI) m/z 437.1 [MH].
94%	With triethylamine In N,N-dimethyl-formamide at 20℃; for 24 h;	2 (3.5 g, 18.0 mmol) was dissolved in DMF (70 mL),Triethylamine (3.0 mL, 21.6 mmol) was added dropwise,Trityl chloride (5.5 g, 19.7 mmol) was added,After 24 hours at room temperature,Poured into 200mL water,Precipitation of a large number of solids,Suction filtration,Ether filtered and washed,Drying gives a white solid,Yield 94.0percent
93%	With triethylamine In DMF (N,N-dimethyl-formamide) at 20℃; for 48 h;	To a solution of 4-iodoimidazole (50 g, 258 mmoles) in DMF (500 ml) was added triethyl amine (37.7 ml, 270.6 mmoles) and than triphenylmethyl chloride (69.7 g, 250 mmoles). After stirring at room temperature for 48 hours, the solution was poured into ice water (2.5 L). The solid was filtered and pumped on for several hours to yield the crude compound. Ethyl ether (200 ml) was added to the crude compound and the solution was filtered to yield 4-IODO-1-TRITYL-LH-IMIDAZOLE (104.1, 93percent) as a white solid. ME (437)

93%	With triethylamine In DMF (N,N-dimethyl-formamide) at 20℃; for 48 h;	To a solution of 4-iodoimidazole (50 g, 258 mmoles) in DMF (500 ML) was added triethyl amine (37.7 ml, 270.6 mmoles) and than triphenylmethyl chloride (69.7 g, 250 mmoles). After stirring at room temperature for 48 hours, the solution was poured into ice water (2.5 L). The solid was filtered and pumped on for several hours to yield the crude compound. Ethyl ether (200 ml) was added to the crude compound and the solution was filtered to yield 4-IODO-1-TRITYL-LH-IMIDAZOLE (104.1, 93percent) as a white solid. MH+ (437)
93%	With triethylamine In dichloromethane at 25℃; for 17 h; Cooling with ice; Inert atmosphere	After dissolving 4-iodo -1Himidazole(compound 1) (1.9g, 10mmol) in dichloromethane (40mL), under ice-cooling,triethylamine (2.1mL, 15mmol), trityl chloride (3.4g, 12mmol) It was added, under argon, andstirred for 17 hours at room temperature (25 ° C). After completion of the reaction, water wasadded, and the mixture was extracted twice with dichloromethane. The combineddichloromethane layers were dried anhydrous sodium sulfate and concentrated under reducedpressure, silica and the resulting crude product was gel column chromatography (eluent:chloroform / n-hexane = 1/1 → chloroform) at Purification, Compound 2 It was obtained (4.1g,9.3mmol, 93percent yield).
93%	With triethylamine In dichloromethane at 25℃; for 17 h; Inert atmosphere	4-Iodo-1H-imidazole (Compound 25, manufactured by Wako Pure Chemical Industries, Ltd.) (1.9 g, 10 mmol) was dissolved in dichloromethane (40 mL)Triethylamine (2.1 mL, 15 mmol) and trityl chloride (3.4 g, 12 mmol) were added and the mixture was stirred at room temperature (25 ° C.) for 17 hours under an argon gas atmosphere. After completion of the reaction, water was added and the mixture was extracted twice with dichloromethane. The combined dichloromethane layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained crude product was purified by silica gel column chromatography (eluent: chloroform / n-hexane = 1/1 → chloroform) to obtain compound 26 (4.1 g, 9.3 mmol, yield 93percent).
93%	With triethylamine In dichloromethane at 25℃; for 17 h; Inert atmosphere	4-iodo-1H-imidazole (Compound 13, manufactured by Wako Pure Chemical Industries, Ltd.) (1.9 g, 10 mmol) was dissolved in dichloromethane (40 mL)below freezing,Triethylamine (2.1 mL, 15 mmol),Trityl chloride (3.4 g, 12 mmol) was added,Under an argon gas atmosphere,And the mixture was stirred at room temperature (25 ° C.) for 17 hours.After completion of the reaction,Add water,Extraction was carried out twice with dichloromethane.The combined dichloromethane layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure,The obtained crude product was purified by silica gel column chromatography (eluent (volume ratio): chloroform / n-hexane = 1/1 → chloroform) to obtain Compound 14 (4.1 g, 9.3 mmol, yield 93percent).
92%	at 20℃; for 24 h;	To a solution of 4-iodoimidazole (1 eq) in DMF at room temperature was added triphenylmethyl chloride (1.2 eq). After stirring at room temperature for 24 h, the solution was poured into ice water and left stirring for 30 min. The solid was filtered and pumped on for several hours to yield the crude compound. Ethyl ether was added to the crude compound and the solution was filtered to yield 4-iodo-1- TRITYL-LH-IMIDAZOLE (92percent) as a white solid. MH+ (437).
92%	Stage #1: With triethylamine In N,N-dimethyl-formamide at 0℃; for 0.166667 h; Stage #2: at 20℃; for 16 h;	At 0° C., to a solution of 4-iodo-1H-imidazole (5 g, 25.8 mmol) in DMF (100 mL) was added triethylamine (3.13 g, 30.9 mmol) slowly. After stirring for additional 10 min at 0° C., the reaction mixture was added by TrtCl (7.17 g, 25.7 mmol). The resulting solution was then stirred at room temperature for 16 h. The reaction mixture was poured into 1 L water. A white solid precipitated out and were collected by filtration. The solid was rinsed with MeOH (50 mL×2) and Et₂O (50 mL×3), and then dried in vacuo to yield 4-iodo-1-(triphenylmethyl)-1H-imidazole as white solid (10.4 g, 92percent).
90%	at 0 - 20℃;	4-lodo-1tf-imidazole (2.8g, 14.6mmol) and trityl chloride (5.Og, 20.5mmol) were dissolved in λ/,λ/-dimethylacetamide (45mL). The solution was cooled to 0"C and triethylamine (4mL, 29.2mmol) added slowly. The reaction mixture was slowly warmed to room temperature. After 48 hours the solution was poured to water(15OmL). The solid was filtered, washed with water, hexane and dried to give a white solid (5.7g) with a yield of 90percent. The product was pure enough for the next step reaction without further purification.
88.9%	With triethylamine In N,N-dimethyl-formamide at 20℃; for 48 h;	4-iodo-1H-imidazole (20 g, 103 mmoles) was dissolved in DMF (100 mL) then triethylamine (15.1 mL, 108 mmoles) and triphenylmethyl chloride (27.8 g, 100 mmoles). The reaction mixture was stirred at room temperature for 48 h, then poured into ice water (500 mL), and then evaporated to dryness, and filtered, and dried to give white crystals of 4-iodo-1-triphenylmethyl-1H-imidazole (40 g, 91.7 mmol, 88.9percent).
81%	With triethylamine In tetrahydrofuran at 70℃; for 3 h; Inert atmosphere	Triethylamine (36.0 mL, 258 mmol) was added to a mixture of 4-iodoimidazole (24.8 g, 128 mmol) and trityl chloride (39.2 g, 141 mmol) in THF (275 mL), the resulting mixture was heated at 70 °C for 3 hours under nitrogen. The reaction was cooled to 45 °C and filtered to remove thesuspended white solid (Et3N.HCI). The filtrate was concentrated in vacuo, dissolved in DCM (500 mL) and washed with 5 wtpercent aq. sodium thiosulfate solution (300 mL). The aqueous layer was extracted with DCM (150 mL). The combined organics were dried over Na2SO4, filtered and concentrated in vacuo to afford an off white solid. Hot filtration was carried out with methanol (500 ml) at 90°C to afford a white solid characterised as 4-iodo-1-trityl-imidazole (45.2 g, 104 mmol, 81percentyield). 1H NMR (CDCI3, 400 MHz) O: 7.36-7.44 (m, 9H), 7.28-7.32 (m, 1H), 7.10-7.15 (m, 6H), 6.94 (5, 1 H). LCMS purity >95percent, [M+H] = 437.0, 4.47 mm (analytical long).
71%	With triethylamine In tetrahydrofuran at 80℃;	4-Iodoimidazole (0101-1) (10.0 g, 51.6 mmol, 1.0 eq.)Dissolved in 150 ml of tetrahydrofuran,Triphenylmethyl chloride (17.2 g, 61.7 mmol, 1.2 equivalents) andTriethylamine (14.5 ml, 10.4 mmol, 2.0 eq),Heat to 80°C and react overnight.Cooled to room temperature, concentrated under reduced pressure, added ethyl acetate, washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Methanol and a small amount of dichloromethane were added and stirred for half an hour. The solid was collected by suction, washed twice with methanol, and vacuum dried. ,4-Iodo-1-trityl-1H-imidazole (16 g, yield: 71percent) was obtained as a white solid.
66%	With triethylamine In N,N-dimethyl-formamide at 20℃; for 14 h;	After dissolving 4-iodo-1H-imidazole (3.0 g, 0.015 mol) and triphenylmethyl chloride (6.0 g, 0.021 mol) in anhydrous N, N-dimethylformamide (50 mL) Deg.] C, triethylamine (7.2 mL, 0.052 mol) was added slowly, and the mixture was stirred at room temperature for 14 hours. The reaction mixture was concentrated, and then distilled water (100 mL) was added thereto. After stirring at room temperature for 20 minutes, the solid was filtered The filtrate was washed with distilled water and diethyl ether to give the title compound 60-a (4.4 g, 66percent) as a white solid.
59%	With triethylamine In water; N,N-dimethyl-formamide	Preparation 72 4-Iodo-1-triphenylmethyl-1H-imidazole To 4-iodo-1H-imidazole (Preparation 71, 3.0 g, 15.3 mmol) in N,N-dimethylformamide (25 ml) was added triphenylmethyl chloride (4.72 g, 16.9 mmol) and then triethylamine (2.5 ml, 18.4 mmol). After stirring at room temperature for 2.5 h, water (200 ml) was added and the reaction mixture was filtered and washed with water. The crude solid was chromatographed on silica gel eluding with hexane:ethyl acetate (5:1 and then 2:1). The material was then recrystallized from hexane and dichloromethane to give the title compound as a white solid (4.0 g, 59percent). NMR (CDCl₃, selected data for the free base: 6.9 (m, 1H), 7.0-7.2 (m, 6H), 7.25-7.4 (m, 10H). MS (TSP): M/Z (MH⁺): 436.3; C₂₂H₁₇¹²⁹IN₂+H requires 437.1.
55.57%	With triethylamine In tetrahydrofuran at 70℃; for 3 h;	4-iodoimidazole (5.38g, 27.72mmol) was dissolved in THF (86ml_). Trityl chloride, (8.5g, 30.49mmol) and triethylamine (7.73ml_, 55.44mmol) were added and the reaction was heated at 70 °C. After 3 h, TLC showed that the reaction had gone to completion. Therefore, the reaction mixture was allowed to cool to 45 C and filtered to remove the suspended white solid. The filtrate was concentrated, redissolved in DCM (300 mL) and washed with 5 wtpercent aq. sodium thiosulfate solution (300 mL), which was back-extracted with DCM (150 mL). The organics were combined, dried over sodium sulfate, filtered and concentrated to yield the crude product. The white solid was taken up in EtOAc (300ml) and heated to reflux for 30 minutes. The mixture was cooled and the solid was obtained by vacuum filtration. The white solid was dried in the vacuum oven for 3 hours affording 4- iodo-1 -trityl-imidazole (6.721 g, 15.40mmol, 55.57percent yield). MS Method 2: RT 2.08 min, ES⁺ m/z 459 [M+Na]⁺ H NMR (400MHz, DMSO) δ/ppm: 7.35-7.40 (m, 10H), 7.06-7.1 1 (m, 7H).

Reference： [1] Journal of Heterocyclic Chemistry, 1985, vol. 22, p. 57 - 59
[2] European Journal of Medicinal Chemistry, 2017, vol. 140, p. 293 - 304
[3] Patent: CN107501272, 2017, A, . Location in patent: Paragraph 0085; 0086; 0091; 0092
[4] Patent: WO2004/96822, 2004, A2, . Location in patent: Page 262
[5] Patent: WO2004/96823, 2004, A2, . Location in patent: Page 44; 45
[6] Patent: JP2015/93833, 2015, A, . Location in patent: Paragraph 0057; 0058
[7] Patent: JP2015/93831, 2015, A, . Location in patent: Paragraph 0016; 0100; 0101
[8] Patent: JP2015/110563, 2015, A, . Location in patent: Paragraph 0016; 0078; 0079
[9] Patent: WO2004/96822, 2004, A2, . Location in patent: Page 239; 240
[10] Patent: US2016/75711, 2016, A1, . Location in patent: Paragraph 0216-0217
[11] Patent: WO2009/93981, 2009, A1, . Location in patent: Page/Page column 96
[12] Patent: CN108203438, 2018, A, . Location in patent: Paragraph 0142; 0143; 0144; 0145
[13] Patent: WO2016/59412, 2016, A1, . Location in patent: Paragraph 00200; 00201
[14] Synthesis, 1994, # 7, p. 681 - 682
[15] Patent: CN107383024, 2017, A, . Location in patent: Paragraph 0112
[16] Patent: KR101798840, 2017, B1, . Location in patent: Paragraph 1139-1142
[17] Journal of Medicinal Chemistry, 2008, vol. 51, # 10, p. 2944 - 2953
[18] Patent: US6313312, 2001, B1,
[19] Patent: WO2016/55786, 2016, A1, . Location in patent: Paragraph 00231
[20] Journal of Medicinal Chemistry, 1996, vol. 39, # 15, p. 3001 - 3013
[21] Journal of Organic Chemistry, 2007, vol. 72, # 10, p. 3741 - 3749
[22] Patent: US5932606, 1999, A,
[23] Patent: US2002/19527, 2002, A1,

8
[ 71759-89-2 ]
[ 60-29-7 ]
[ 76-83-5 ]
[ 96797-15-8 ]

Reference： [1] Patent: US2003/125266, 2003, A1,

9
[ 5779-93-1 ]
[ 96797-15-8 ]
[ 176721-01-0 ]

Yield	Reaction Conditions	Operation in experiment
84%	Stage #1: With isopropylmagnesium bromide In tetrahydrofuran; dichloromethane at 10 - 20℃; for 1 h; Stage #2: at 10 - 25℃; for 1 h;	Example 1 (step a); Preparation of (2,3-Dimethylphenyl)-(3-trityl-3H-imidazol-4-yl)methanol A solution of isopropylmagnesium bromide in tetrahydrofuran (48 mL, 0.046 mol) was added to a stirred solution of 4-iodo-1-trityl-1 H-imidazole (19.0 g, 0.046 mol) in dichloromethane (180 mL) at 10 to 15°C. The reaction mixture was allowed to warm to the ambient temperature and was stirred at ambient temperature for 1 hour. The reaction mixture was then cooled to 10-15°C, at which point a solution of 2,3-dimethylbenzaldehyde (6.2 mL, 0.046 mol) in dichloromethane (10 mL) was added, while not exceeding 20 to 25°C. After additional stirring for 1 hour at ambient temperature a 10percent aqueous ammonium chloride solution (200 mL) was added to the reaction mixture. The organic layer was separated and washed with an aqueous sodium chloride solution (150 mL), thereafter the organic layer was concentrated to a volume of 40 mL. A precipitate of (2,3-dimethylphenyl)-(3-trityl-3H-imidazol-4-yl)methanol was obtained upon cooling the distillation residue to 4°C and it was separated by filtration, then washed with dichloromethane (50 mL). The intermediate (2,3-dimethylphenyl)-(3-trityl-3H-imidazol-4-yl)methanol was dried at ambient temperature. The yield was 17.4 g (84 percent) of a white or off-white powder, having a melting temperature of 203.0 to 207.0°C.

Reference： [1] Patent: EP1918282, 2008, A1, . Location in patent: Page/Page column 5

10
[ 96797-15-8 ]
[ 1402836-58-1 ]

Reference： [1] Tetrahedron, 2018, vol. 74, # 24, p. 3045 - 3051

[ 96797-15-8 ] Synthesis Path-Downstream 1~69

1
[ 71759-89-2 ]
[ 76-83-5 ]
[ 96797-15-8 ]

Yield	Reaction Conditions	Operation in experiment
94%	With triethylamine; In N,N-dimethyl-formamide; at 20℃; for 24h;	To a solution of 3 (3.5 g,18.0 mmol) in DMF (70 mL) was added TEA (3.0 mL, 21.7 mmol) andtrityl chloride (5.5 g, 19.7 mmol). After stirring at 20 C for 24 h, thesolution was poured into water. The solid was filtered to yield thecrude compound that was purified by flash column chromatographyon silica gel to afford 4 as a white solid (7.4 g, 94.0%). Mp148e150 C. 1H NMR (300 MHz, Chloroform-d) d(ppm) 6.9 (m, 1H),7.0e7.2 (m, 6H), 7.25e7.4 (m, 10H). MS (EI) m/z 437.1 [MH].
94%	With triethylamine; In N,N-dimethyl-formamide; at 20℃; for 24h;	2 (3.5 g, 18.0 mmol) was dissolved in DMF (70 mL),Triethylamine (3.0 mL, 21.6 mmol) was added dropwise,Trityl chloride (5.5 g, 19.7 mmol) was added,After 24 hours at room temperature,Poured into 200mL water,Precipitation of a large number of solids,Suction filtration,Ether filtered and washed,Drying gives a white solid,Yield 94.0%
93%	With triethylamine; In DMF (N,N-dimethyl-formamide); at 20℃; for 48h;	To a solution of <strong>[71759-89-2]4-iodoimidazole</strong> (50 g, 258 mmoles) in DMF (500 ml) was added triethyl amine (37.7 ml, 270.6 mmoles) and than triphenylmethyl chloride (69.7 g, 250 mmoles). After stirring at room temperature for 48 hours, the solution was poured into ice water (2.5 L). The solid was filtered and pumped on for several hours to yield the crude compound. Ethyl ether (200 ml) was added to the crude compound and the solution was filtered to yield 4-IODO-1-TRITYL-LH-IMIDAZOLE (104.1, 93%) as a white solid. ME (437)

93%	With triethylamine; In DMF (N,N-dimethyl-formamide); at 20℃; for 48h;	To a solution of <strong>[71759-89-2]4-iodoimidazole</strong> (50 g, 258 mmoles) in DMF (500 ML) was added triethyl amine (37.7 ml, 270.6 mmoles) and than triphenylmethyl chloride (69.7 g, 250 mmoles). After stirring at room temperature for 48 hours, the solution was poured into ice water (2.5 L). The solid was filtered and pumped on for several hours to yield the crude compound. Ethyl ether (200 ml) was added to the crude compound and the solution was filtered to yield 4-IODO-1-TRITYL-LH-IMIDAZOLE (104.1, 93%) as a white solid. MH+ (437)
93%	With triethylamine; In dichloromethane; at 25℃; for 17h;Cooling with ice; Inert atmosphere;	After dissolving 4-iodo -1Himidazole(compound 1) (1.9g, 10mmol) in dichloromethane (40mL), under ice-cooling,triethylamine (2.1mL, 15mmol), trityl chloride (3.4g, 12mmol) It was added, under argon, andstirred for 17 hours at room temperature (25 C). After completion of the reaction, water wasadded, and the mixture was extracted twice with dichloromethane. The combineddichloromethane layers were dried anhydrous sodium sulfate and concentrated under reducedpressure, silica and the resulting crude product was gel column chromatography (eluent:chloroform / n-hexane = 1/1 ? chloroform) at Purification, Compound 2 It was obtained (4.1g,9.3mmol, 93% yield).
93%	With triethylamine; In dichloromethane; at 25℃; for 17h;Inert atmosphere;	4-Iodo-1H-imidazole (Compound 25, manufactured by Wako Pure Chemical Industries, Ltd.) (1.9 g, 10 mmol) was dissolved in dichloromethane (40 mL)Triethylamine (2.1 mL, 15 mmol) and trityl chloride (3.4 g, 12 mmol) were added and the mixture was stirred at room temperature (25 C.) for 17 hours under an argon gas atmosphere. After completion of the reaction, water was added and the mixture was extracted twice with dichloromethane. The combined dichloromethane layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained crude product was purified by silica gel column chromatography (eluent: chloroform / n-hexane = 1/1 ? chloroform) to obtain compound 26 (4.1 g, 9.3 mmol, yield 93%).
93%	With triethylamine; In dichloromethane; at 25℃; for 17h;Inert atmosphere;	<strong>[71759-89-2]4-iodo-1H-imidazole</strong> (Compound 13, manufactured by Wako Pure Chemical Industries, Ltd.) (1.9 g, 10 mmol) was dissolved in dichloromethane (40 mL)below freezing,Triethylamine (2.1 mL, 15 mmol),Trityl chloride (3.4 g, 12 mmol) was added,Under an argon gas atmosphere,And the mixture was stirred at room temperature (25 C.) for 17 hours.After completion of the reaction,Add water,Extraction was carried out twice with dichloromethane.The combined dichloromethane layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure,The obtained crude product was purified by silica gel column chromatography (eluent (volume ratio): chloroform / n-hexane = 1/1 ? chloroform) to obtain Compound 14 (4.1 g, 9.3 mmol, yield 93%).
92%	In DMF (N,N-dimethyl-formamide); at 20℃; for 24h;	To a solution of <strong>[71759-89-2]4-iodoimidazole</strong> (1 eq) in DMF at room temperature was added triphenylmethyl chloride (1.2 eq). After stirring at room temperature for 24 h, the solution was poured into ice water and left stirring for 30 min. The solid was filtered and pumped on for several hours to yield the crude compound. Ethyl ether was added to the crude compound and the solution was filtered to yield 4-iodo-1- TRITYL-LH-IMIDAZOLE (92%) as a white solid. MH+ (437).
92%		At 0 C., to a solution of <strong>[71759-89-2]4-iodo-1H-imidazole</strong> (5 g, 25.8 mmol) in DMF (100 mL) was added triethylamine (3.13 g, 30.9 mmol) slowly. After stirring for additional 10 min at 0 C., the reaction mixture was added by TrtCl (7.17 g, 25.7 mmol). The resulting solution was then stirred at room temperature for 16 h. The reaction mixture was poured into 1 L water. A white solid precipitated out and were collected by filtration. The solid was rinsed with MeOH (50 mL×2) and Et2O (50 mL×3), and then dried in vacuo to yield 4-iodo-1-(triphenylmethyl)-1H-imidazole as white solid (10.4 g, 92%).
90%	In ISOPROPYLAMIDE; at 0 - 20℃;	4-lodo-1tf-imidazole (2.8g, 14.6mmol) and trityl chloride (5.Og, 20.5mmol) were dissolved in lambda/,lambda/-dimethylacetamide (45mL). The solution was cooled to 0"C and triethylamine (4mL, 29.2mmol) added slowly. The reaction mixture was slowly warmed to room temperature. After 48 hours the solution was poured to water(15OmL). The solid was filtered, washed with water, hexane and dried to give a white solid (5.7g) with a yield of 90%. The product was pure enough for the next step reaction without further purification.
88.9%	With triethylamine; In N,N-dimethyl-formamide; at 20℃; for 48h;	<strong>[71759-89-2]4-iodo-1H-imidazole</strong> (20 g, 103 mmoles) was dissolved in DMF (100 mL) then triethylamine (15.1 mL, 108 mmoles) and triphenylmethyl chloride (27.8 g, 100 mmoles). The reaction mixture was stirred at room temperature for 48 h, then poured into ice water (500 mL), and then evaporated to dryness, and filtered, and dried to give white crystals of 4-iodo-1-triphenylmethyl-1H-imidazole (40 g, 91.7 mmol, 88.9%).
88%	With triethylamine; In dichloromethane; at 20℃; for 15h;	To a stirred suspension of compound 40 (5.00 g, 25.78 mmol), Triphenylmethyl chloride (8.63 g, 30.94 mmol) in DCM (100 mL) was added TEA (3.91 g, 38.67 mmol), the resulting mixture was stirred at rt for 15 h, TLC showed that the start materials was consumed up, stopped the reaction, poured into a mixture of DCM (200 mL) and H20 (150 mL), the organic layer was separated and washed with brine, dried over anhydrous Na2S04, concentrate in vacuo, the residue was purified by column (EtOAc/Hex 1/30 to 1/5) to give compound 41 (10.00 g, 88% yield) as a white solid. MS (ESI) (M/Z): [M+H]+ =437.0; 1H NMR (400 MHz, CDCI3) delta 7.41 - 7.34 (m, 10H), 7.18 - 7.11 (m, 6H), 6.94 (d, = 1.4 Hz, 1H).
81%	With triethylamine; In tetrahydrofuran; at 70℃; for 3h;Inert atmosphere;	Triethylamine (36.0 mL, 258 mmol) was added to a mixture of <strong>[71759-89-2]4-iodoimidazole</strong> (24.8 g, 128 mmol) and trityl chloride (39.2 g, 141 mmol) in THF (275 mL), the resulting mixture was heated at 70 C for 3 hours under nitrogen. The reaction was cooled to 45 C and filtered to remove thesuspended white solid (Et3N.HCI). The filtrate was concentrated in vacuo, dissolved in DCM (500 mL) and washed with 5 wt% aq. sodium thiosulfate solution (300 mL). The aqueous layer was extracted with DCM (150 mL). The combined organics were dried over Na2SO4, filtered and concentrated in vacuo to afford an off white solid. Hot filtration was carried out with methanol (500 ml) at 90C to afford a white solid characterised as 4-iodo-1-trityl-imidazole (45.2 g, 104 mmol, 81%yield). 1H NMR (CDCI3, 400 MHz) O: 7.36-7.44 (m, 9H), 7.28-7.32 (m, 1H), 7.10-7.15 (m, 6H), 6.94 (5, 1 H). LCMS purity >95%, [M+H] = 437.0, 4.47 mm (analytical long).
78%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;	4-Iodo-1H-imidazole (5 g, 25.8 mmol) and N,N-diisopropylethylamine (6.65 g, 51.5 mmol) wereadded to dry dimethylformamide (30 mL), and (chloromethanetriyl)tribenzene (7.89 g, 28.4 mmol)was added to reaction mixture gradually at 20 C. After the reaction mixture was stirred at 20 Cuntil the starting material disappeared in thin layer chromatography (TLC), the reaction mixture wasdistilled in vacuo, ethyl acetate (200 mL) was added to the mixture. The organic extract was washedtwice with saturated aqueous NaCl (40 mL), and the organic extract was dried over Na2SO4. Aftersolvent was removed under vacuum, the product was purified as a white solid by silica gel columnchromatography, 8.77 g, yield 78%. 1H-NMR (400 MHz, CDCl3): = 7.38-7.33 (m, 10H, H-phenyl,H-imidazolyl), 7.13-7.09 (m, 6H, H-phenyl), 6.92 (d, J = 1.4 Hz, 1H, H-imidazolyl). 13C-NMR (101 MHz,CDCl3): = 141.83, 140.56, 129.72 (6C), 128.29 (3C), 128.18 (6C), 127.91, 126.89 (3C), 75.84. HRMS (ESI):m/z [M + H]+ calculated for C22H18N2I: 437.05092; found: 437.04934.
71%	With triethylamine; In tetrahydrofuran; at 80℃;	4-Iodoimidazole (0101-1) (10.0 g, 51.6 mmol, 1.0 eq.)Dissolved in 150 ml of tetrahydrofuran,Triphenylmethyl chloride (17.2 g, 61.7 mmol, 1.2 equivalents) andTriethylamine (14.5 ml, 10.4 mmol, 2.0 eq),Heat to 80C and react overnight.Cooled to room temperature, concentrated under reduced pressure, added ethyl acetate, washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Methanol and a small amount of dichloromethane were added and stirred for half an hour. The solid was collected by suction, washed twice with methanol, and vacuum dried. ,4-Iodo-1-trityl-1H-imidazole (16 g, yield: 71%) was obtained as a white solid.
66%	With triethylamine; In N,N-dimethyl-formamide; at 20℃; for 14h;	After dissolving <strong>[71759-89-2]4-iodo-1H-imidazole</strong> (3.0 g, 0.015 mol) and triphenylmethyl chloride (6.0 g, 0.021 mol) in anhydrous N, N-dimethylformamide (50 mL) Deg.] C, triethylamine (7.2 mL, 0.052 mol) was added slowly, and the mixture was stirred at room temperature for 14 hours. The reaction mixture was concentrated, and then distilled water (100 mL) was added thereto. After stirring at room temperature for 20 minutes, the solid was filtered The filtrate was washed with distilled water and diethyl ether to give the title compound 60-a (4.4 g, 66%) as a white solid.
59%	With triethylamine; In water; N,N-dimethyl-formamide;	Preparation 72 4-Iodo-1-triphenylmethyl-1H-imidazole To <strong>[71759-89-2]4-iodo-1H-imidazole</strong> (Preparation 71, 3.0 g, 15.3 mmol) in N,N-dimethylformamide (25 ml) was added triphenylmethyl chloride (4.72 g, 16.9 mmol) and then triethylamine (2.5 ml, 18.4 mmol). After stirring at room temperature for 2.5 h, water (200 ml) was added and the reaction mixture was filtered and washed with water. The crude solid was chromatographed on silica gel eluding with hexane:ethyl acetate (5:1 and then 2:1). The material was then recrystallized from hexane and dichloromethane to give the title compound as a white solid (4.0 g, 59%). NMR (CDCl3, selected data for the free base: 6.9 (m, 1H), 7.0-7.2 (m, 6H), 7.25-7.4 (m, 10H). MS (TSP): M/Z (MH+): 436.3; C22H17129IN2+H requires 437.1.
58%		Et3N (0.59 mL, 4.25 mmol) was added to a solution of <strong>[71759-89-2]4-iodoimidazole</strong> [71759-89-2] (750 mg, 3.87 mmol) in DCM (30 mL). The reaction mixture was stirred at room temperature for 5 min and trytil chloride (1.19 g, 4.25 mmol) was added. The reaction mixture was stirred at 40 C for 16 h. The reaction mixture was diluted with NaHCCh (sat., aq.) and extracted with DCM. The organic layer was dried (MgS04), filtered and the solvent were evaporated in vacuo. The crude mixture was purified by flash column chromatography (silica, heptane/EtOAc, gradient from 100:0 to 60:40) to afford 1-169 (976 mg, 58%).
55.57%	With triethylamine; In tetrahydrofuran; at 70℃; for 3h;	<strong>[71759-89-2]4-iodoimidazole</strong> (5.38g, 27.72mmol) was dissolved in THF (86ml_). Trityl chloride, (8.5g, 30.49mmol) and triethylamine (7.73ml_, 55.44mmol) were added and the reaction was heated at 70 C. After 3 h, TLC showed that the reaction had gone to completion. Therefore, the reaction mixture was allowed to cool to 45 C and filtered to remove the suspended white solid. The filtrate was concentrated, redissolved in DCM (300 mL) and washed with 5 wt% aq. sodium thiosulfate solution (300 mL), which was back-extracted with DCM (150 mL). The organics were combined, dried over sodium sulfate, filtered and concentrated to yield the crude product. The white solid was taken up in EtOAc (300ml) and heated to reflux for 30 minutes. The mixture was cooled and the solid was obtained by vacuum filtration. The white solid was dried in the vacuum oven for 3 hours affording 4- iodo-1 -trityl-imidazole (6.721 g, 15.40mmol, 55.57% yield). MS Method 2: RT 2.08 min, ES+ m/z 459 [M+Na]+ H NMR (400MHz, DMSO) delta/ppm: 7.35-7.40 (m, 10H), 7.06-7.1 1 (m, 7H).
	With triethylamine; In dichloromethane;	Step D 1-Trityl-<strong>[71759-89-2]4-iodoimidazole</strong> Trityl chloride (3.8 g, 13.6 mmol) was added to a cooled (0 C.) solution of <strong>[71759-89-2]4-iodoimidazole</strong> (2.25 g, 11.6 mmol) and triethylamine (2 ml, 14.3 mmol) in methylene chloride (25 ml). After stirring for 30 min the reaction mixture was warmed to room temperature and stirred ther for 2 h. The reaction mixture was washed well with water and saturated NaHCO3 then dried (Na2 SO4). Concentration gave the product as a white solid. 1 H NMR (CDCl3) d 6.92 (s, 1 H), 7.08-7.20 (m, 6 H), 7.28-7.40 (m, 10 H).
	With triethylamine; In N,N-dimethyl-formamide;	EXAMPLE 49A 4-iodo-1-trityl-1H-imidazole A suspension of <strong>[71759-89-2]4-iodoimidazole</strong> (3.38 g, 17.4 mmol) and triphenylmethyl chloride (5.56 g, 19.9 mmol) in DMF (15 mL) at 0 C. was treated with triethylamine (1.5 mL, 10.8 mmol), warmed to room temperature, stirred for 16 hours, poured into ice water, filtered, and dried in a vacuum oven at 50 C. to provide the desired product of sufficient purity for subsequent use without further purification.

Reference： [1]Journal of Heterocyclic Chemistry,1985,vol. 22,p. 57 - 59
[2]European Journal of Medicinal Chemistry,2017,vol. 140,p. 293 - 304
[3]Patent: CN107501272,2017,A .Location in patent: Paragraph 0085; 0086; 0091; 0092
[4]Patent: WO2004/96822,2004,A2 .Location in patent: Page 262
[5]Patent: WO2004/96823,2004,A2 .Location in patent: Page 44; 45
[6]Patent: JP2015/93833,2015,A .Location in patent: Paragraph 0057; 0058
[7]Patent: JP2015/93831,2015,A .Location in patent: Paragraph 0016; 0100; 0101
[8]Patent: JP2015/110563,2015,A .Location in patent: Paragraph 0016; 0078; 0079
[9]Patent: WO2004/96822,2004,A2 .Location in patent: Page 239; 240
[10]Patent: US2016/75711,2016,A1 .Location in patent: Paragraph 0216-0217
[11]Patent: WO2009/93981,2009,A1 .Location in patent: Page/Page column 96
[12]Patent: CN108203438,2018,A .Location in patent: Paragraph 0142; 0143; 0144; 0145
[13]Patent: WO2018/217439,2018,A1 .Location in patent: Page/Page column 40-41
[14]Patent: WO2016/59412,2016,A1 .Location in patent: Paragraph 00200; 00201
[15]Molecules,2019,vol. 24
[16]Synthesis,1994,p. 681 - 682
[17]Patent: CN107383024,2017,A .Location in patent: Paragraph 0112
[18]Patent: KR101798840,2017,B1 .Location in patent: Paragraph 1139-1142
[19]Journal of Medicinal Chemistry,2008,vol. 51,p. 2944 - 2953
[20]Patent: US6313312,2001,B1
[21]Patent: WO2019/243535,2019,A1 .Location in patent: Page/Page column 87
[22]Patent: WO2016/55786,2016,A1 .Location in patent: Paragraph 00231
[23]Journal of Medicinal Chemistry,1996,vol. 39,p. 3001 - 3013
[24]Journal of Organic Chemistry,2007,vol. 72,p. 3741 - 3749
[25]Patent: US5932606,1999,A
[26]Patent: US2002/19527,2002,A1

2
[ 96797-15-8 ]
[ 68-12-2 ]
[ 15469-97-3 ]
4-iodo-2-formyl-1-tritylimidazole [ No CAS ]
[ 67478-50-6 ]
[ 33016-47-6 ]

Reference： [1]Journal of Heterocyclic Chemistry,1985,vol. 22,p. 57 - 59
[2]Journal of Heterocyclic Chemistry,1985,vol. 22,p. 57 - 59

3
[ 778-48-3 ]
[ 96797-15-8 ]
[ 178556-70-2 ]

Reference： [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 3001 - 3013

4
[ 24644-78-8 ]
[ 96797-15-8 ]
[ 192987-46-5 ]

Reference： [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 3014 - 3024

5
[ 6939-35-1 ]
[ 96797-15-8 ]
[ 192987-41-0 ]

Reference： [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 3014 - 3024

6
[ 96797-15-8 ]
[ 105-07-7 ]
[ 169503-34-8 ]

Yield	Reaction Conditions	Operation in experiment
82%		Step 40.a. (R,S) 4-(Hydroxy-(1-trityl-1H-imidazol-4-yl)-methyl)-benzonitrile A solution of 1-trityl-4-iodoimidazole (3.53g, 8.10mmol) in CH2Cl2 (35ml) was cooled to about -3C under N2 and 3M EtMgBr in Et2O was added dropwise while maintaining reaction temperature at below about 0C. The solution was stirred for about one hour at about 0C and then 4-cyanobenzaldehyde (1.18g, 9.00mmol) was added in one portion and the reaction was allowed to warm to room temperature for about 1 hour.. The reaction mixture was then again cooled to about 0C and 5% HCl (30ml) was added.. The reaction mixture was stirred about 15 min. and then extracted with CH2Cl2 (2x25ml).. The combined CH2Cl2 layers were washed with saturated NaHCO3, dried over Na2SO4, filtered, and then concentrated under reduced pressure.. The residue was triturated with EtOAc (25ml) and the product filtered off (2.92g, 82%).. Mass spec. 442.3 MH+, NMR (300MHZ, DMSO-d6, 30C) 7.7-7.8 (2H, d), 7.5-7.6 (2H, d), 7.3-7.5 (9H, m), 7.25-7.3 (1H, s), 7.0-7.15 (6H, m), 6.75-6.8 (1H, s), 5.9-6.90 (1H, m), 5.6-5.7 (1H, m).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 4001 - 4005
[2]Patent: EP1382607,2004,A2 .Location in patent: Page 46
[3]Journal of Medicinal Chemistry,2008,vol. 51,p. 2944 - 2953
[4]Bioorganic and Medicinal Chemistry Letters,1998,vol. 8,p. 2263 - 2268

7
[ 96797-15-8 ]
[ 68-12-2 ]
[ 33016-47-6 ]

Yield	Reaction Conditions	Operation in experiment
73.2%		Example 1 Preparation of 1-trityl-1 H-imidazole-4-carboxaldehyde1-Trityl-4-iodoimidazole (87, 3g, 0,200mol) was added to stirred methylene chloride (525ml_) in a 4-neck round bottom flask fitted with a mechanical stirrer, a thermometer, a dropping funnel and a tube for argon introduction into the reaction mixture. The reaction mixture was cooled to 1O0C, at which point isopropylmagnesium chloride solution in tetrahydrofuran (112ml_, 0,213 mol) was added dropwise <n="7"/>under an argon atmosphere. After addition of isopropylmagnesium chloride the reaction mixture was warmed to 2O0C.N,N-Dimethylformamide (47ml_, 0,608mol) was added to methylene chloride (30OmL) in a 4-neck round bottom flask fitted with a mechanical stirrer, a thermometer, a dropping funnel and a tube for argon introduction into the reaction mixture. The reaction mixture was stirred and cooled to (-5) 0C and solution of the imidazole Grignard derivative, which was prepared above, was added to the reaction mixture. The reaction mixture was stirred at (-5) 0C for half an hour and then at 2O0C for 10 hours, at which point 10% aqueous ammonium chloride solution (30OmL) was added to the reaction mixture.The aqueous layer was extracted with methylene chloride (55OmL). The organic layer was separated and washed with saturated sodium chloride solution, and then the organic layer was stirred with anhydrous magnesium sulphate for 2 hours. The precipitate of magnesium sulphate was separated by filtration. The solvent was removed by distillation at a reduced pressure. Ethanol (20OmL) was added to the distillation residue and the reaction mixture was cooled to (-5)C for 2 hours.The precipitates were separated by filtration. The obtained intermediate 1-trityl- 1 H-imidazole-4-carboxaldehyde was dried at under reduced pressure. The yield was 56.6g (73.2%).

Reference： [1]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 1197 - 1205
[2]Il Farmaco,2003,vol. 58,p. 279 - 283
[3]Patent: WO2009/71584,2009,A1 .Location in patent: Page/Page column 4; 5-6

8
[ 96797-15-8 ]
[ 222978-03-2 ]
[ 275807-74-4 ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 2973 - 2984

9
[ 96797-15-8 ]
[ 101048-76-4 ]
[ 222978-23-6 ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 2973 - 2984

10
[ 56423-63-3 ]
[ 96797-15-8 ]
2-(1-trityl-1H-imidazol-4-yl)-pyrazine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 1730 - 1743

11
[ 3430-13-5 ]
[ 96797-15-8 ]
2-methyl-5-(1-trityl-1H-imidazol-4-yl)-pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of 4-IODO-L-TRITYL-LH-IMIDAZOLE (1 eq) in THF at room temperature was added ethylmagnesium bromide (1.2 eq) under dry conditions. After stirring for 90 minutes, zinc chloride (1.2 eq) was added to the reaction mixture. After stirring for another 90 minutes, tetrakis (triphenylphosphine) palladium (10%) and 5- bromo-2-methylpyridine (1.2 eq) were added to the reaction mixture. Following that, the reaction mixture was heated in a 70C oil bath overnight. Upon cooling, the reaction was diluted with dichloromethane and washed with a EDTA buffer (at approximately pH 9), NaCl, dried over sodium sulfate, filtered and concentrated. The crude product was disolved in ethanol and concentrated HCl was added to the solution at room temperature. The reaction mixture was heated in a 50C oil bath for 2 hours. Upon cooling, the reaction was filtered and washed with ethyl ether to yield 5- (1H- imidazol-4-yl) -2-methyl-pyridine (63%). MH+ (160)
		To a solution of 4-IODO-L-TRITYL-LH- imidazole (15.0 g, 34 mmoles) in THF (150 ml) at room temperature was added ethylmagnesium bromide (41 ml, 40.7 mmoles) under dry conditions. After stirring for 90 minutes, zinc chloride (5.6 g, 40.7 mmoles) was added to the reaction mixture. After stirring for another 90 minutes, tetrakis (RIPHENYLPHOSPHINE) palladium (4.0 g, 3.43 mmoles) and 5-bromo-2-methylpyridine (7.0 g, 40.7 mmoles) were added to the reaction mixture. Following that, the reaction mixture was heated in a 70C oil bath overnight. Upon cooling, the reaction was diluted with dichloromethane and washed with an EDTA buffer (at APPROIMATE pH 9) (2x 300 ML), NACI (sat. ) (300 ml), dried over sodium sulfate, filtered, and concentrated. The crude product was dissolved in ethanol (250 ml) and concentrated HCl (13.6 ml) was added to the solution at room temperature. The reaction mixture was heated in a 50C oil bath for 2 hours. Upon cooling, the reaction was filtered and washed with ethyl ether (25 ml) to yield 5- (1H- imidazol-4-yl) -2-methyl-pyridine (5.815g, 63%). MH+ (160).

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 1730 - 1743
[2]Patent: WO2004/96822,2004,A2 .Location in patent: Page 240; 262; 263
[3]Patent: WO2004/96823,2004,A2 .Location in patent: Page 45; 46

12
[ 4595-59-9 ]
[ 96797-15-8 ]
5-(1-trityl-1H-imidazol-4-yl)-pyrimidine dihydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of 4-iodo-1-trityl-lH-imidazole (A) (1 eq) in THF (100 ml) at room temperature was added ethylmagnesium bromide (1.2 eq) under dry conditions. After stirring for 90 minutes, zinc chloride (1.2 eq) was added to the reaction mixture. After stirring for another 90 minutes, tetrakis (triphenylphosphine) palladium (10%) and 5-bromopyrimidine (1.2 eq) were added to the reaction mixture. Subsequent reaction conditions and work up are as described previously in Example 73, the resulting solid 5-(LH-IMIDAZOL-4-YL)-PYRIMIDINE (46%) was collected by filtration and used without further purification. MH+ (147)

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 1730 - 1743
[2]Patent: WO2004/96822,2004,A2 .Location in patent: Page 243

13
[ 53939-30-3 ]
[ 96797-15-8 ]
2-chloro-5-(1-trityl-1H-imidazol-4-yl)-pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		A. 5- (LH-IMIDAZOL-4-YL)-2-CHLORO-PYRIDINE. To a solution OF 4-IODO-1- TRITYL-LH-IMIDAZOLE (72.8 g, 166 mmoles) in THF (400 ml) at room temperature was added ethylmagnesium bromide (200 ml, 200 mmoles) under dry conditions. After stirring for 90 minutes, zinc chloride (27.2 g, 200 mmoles) was added to the reaction mixture. After stirring for another 90 minutes, tetrakis (triphenylphosphine) palladium (20 g, 16.6 mmoles) and 5-bromo-2-chloropyridine (38. 48 g, 200 mmoles) were added to the reaction mixture. Following that, the reaction mixture was heated in a 70C oil bath overnight. Upon cooling, the reaction was diluted with dichloromethane (1 L) and washed with a 30% NaOH solution containing an added 40 g of EDTA (3x 400 ml), with NACI (sat. ) (300 ml), dried over MGS04, filtered, and concentrated. To the crude material was added dichloromethane (600 ml) and trifluoroactetic acid (180 ml). After standing for 1 hour, the reaction was concentrated and pumped on overnight. To the resulting oily tar was added 1M HCl (100 ml) and the mixture was sonicated for 30 minutes and than filtered. The aqueous filtrate was washed with diethyl ether (400 ml). The ether layer was back extracted with 1 M HCL (2x 20 ml). The combined aqueous layers were washed with diethyl ether (2x 200 ml). The aqueous layer was cooled in an ice bath and the pH was adjusted by addition of a 30% NaOH solution until the pH was around 9-10. The resulting solid was filtered, rinsed with cold water (20 ml), rinsed with diethyl ether (20 ml), and pumped on yielding 5- (LH-IMIDAZOL-4-YL)-2-CHLORO-PYRIDINE (12.90 g, 43%). MH+ (180)
		To a solution of 4-IODO-1-TRITYL-LH- imidazole (72.8 g, 166 mmoles) in THF (400 ML) at room temperature was added ethylmagnesium bromide (200 ml, 200 mmoles) under dry conditions. After stirring for 90 minutes, zinc chloride (27.2 g, 200 mmoles) was added to the reaction mixture. After stirring for another 90 minutes, tetrakis (triphenylphosphine) palladium (20 g, 16.6 mmoles) and 5-bromo-2-chloropyridine (38.48 g, 200 mmoles) were added to the reaction mixture. Following that, the reaction mixture was heated in a 70C oil bath overnight. Upon cooling, the reaction was diluted with dichloromethane (1 L) and washed with a 30% NaOH solution containing an added 40 g of EDTA (3x 400 ml), with NACI (sat. ) (300 ml), dried over MGS04, filtered, and concentrated. To the crude material was added dichloromethane (600 ml) and trifluoroactetic acid (180 ml). After standing for 1 hour, the reaction was concentrated and pumped on overnight. To the resulting oily tar was added 1M HC1 (100 ml) and the mixture was sonicated for 30 minutes and than filtered. The aqueous filtrate was washed with diethyl ether (400 ml). The ether layer was back extracted with 1M HC1 (2x 20 ml). The combined aqueous layers were washed with diethyl ether (2x 200 ml). The aqueous layer was cooled in an ice bath and the pH was adjusted by addition of a 30% NaOH solution until the pH was around 9-10. The resulting solid was filtered, rinsed with cold water (20 ml), rinsed with diethyl ether (20 ml), and pumped on yielding 5- (1H- IMIDAZOL-4-YL)-2-CHLORO-PYRIDINE (12.90 g, 43%). MH+ (180).

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 1730 - 1743
[2]Patent: WO2004/96822,2004,A2 .Location in patent: Page 268; 269
[3]Patent: WO2004/96823,2004,A2 .Location in patent: Page 50; 51

14
[ 13472-85-0 ]
[ 96797-15-8 ]
[ 484673-50-9 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of 4-IODO-1-TRITYL-LH-IMIDAZOLE (A) (1 eq) in THF at room temperature was added ethylmagnesium bromide (1.2 eq) under dry conditions. After stirring for 90 minutes, zinc chloride (1.2 eq) was added to the reaction mixture. After stirring for another 90 minutes, tetrakis (triphenylphosphine) palladium (10%) and 5-bromo-2-methoxypyridine (1.2 eq) were added to the reaction mixture. Upon cooling, the reaction was diluted with dichloromethane and washed with a EDTA buffer (at approximate pH 9), NACI (sat. ), dried over sodium sulfate, filtered, and concentrated. MH+ (418)
		A. 5-imidazol-4-yl-2-methoxypyridine. To a solution of 4-IODO-1- TRITYL-LH-IMIDAZOLE (25 g, 57.2 mmoles) in THF (150 ml) at room temperature was added ethylmagnesium bromide (69 ml, 68.7 mmoles) under dry conditions. After stirring for 90 minutes, zinc chloride (9.4 g, 68.6 mmoles) was added to the reaction mixture. After stirring for another 90 minutes, tetrakis (triphenylphosphine) palladium (6.6 g, 5.72 mmoles) and 5-BROMO-2-METHOXYPYRIDINE (8.9 ml, 68.7 mmoles) were added to the reaction mixture. Following that, the reaction mixture was heated in a 70C oil bath overnight. Upon cooling, the reaction was diluted with dichloromethane (500 ml) and washed with a 30% NaOH solution containing an added 20 g of EDTA (3x 200 ml), with NACI (sat. ) (200 ml), dried over MGS04, filtered, and concentrated. To the crude material was added dichloromethane (200 ml) and trifluoroactetic acid (40 ml, 410 mmoles). After standing for 6 hours, the reaction was concentrated and pumped on overnight. The crude material was purified by flash chromatography using 0-5% MEOH/CH2CL2 with 0.1% triethylamine yielding 5-imidazol-4-yl-2- methoxypyridine (7. 0g, 70%). MH+ (176)
		To a solution OF 4-IODO-1-TRITYL-LH-IMIDAZOLE (25 g, 57.2 mmoles) in THF (150 ML) at room temperature was added ethylmagnesium bromide (69 ml, 68. 7 mmoles) under dry conditions. After stirring for 90 minutes, zinc chloride (9.4 g, 68.6 mmoles) was added to the reaction mixture. After stirring for another 90 minutes, tetrakis (triphenylphosphine) palladium (6.6 g, 5.72 mmoles) and 5-BROMO-2-METHOXYPYRIDINE (8.9 ml, 68. 7 mmoles) were added to the reaction mixture. Following that, the reaction mixture was heated in a 70C oil bath overnight. Upon cooling, the reaction was diluted with dichloromethane (500 ml) and washed with a 30% NaOH solution containing an added 20 g of EDTA (3x 200 ML), with NaCl (sat. ) (200 ml), dried over MGS04, filtered, and concentrated. To the crude material was added dichloromethane (200 ml) and trifluoroactetic acid (40 ml, 410 mmoles). After standing for 6 hours, the reaction was concentrated and pumped on overnight. The crude material was purified by flash chromatography using 0-5% MEOH/CH2CL2 with 0.1% triethylamine yielding 5-imidazol-4-yl-2-methoxypyridine (7. 0g, 70%). MH (176)

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 1730 - 1743
[2]Patent: WO2004/96822,2004,A2 .Location in patent: Page 245
[3]Patent: WO2004/96822,2004,A2 .Location in patent: Page 266; 267
[4]Patent: WO2004/96823,2004,A2 .Location in patent: Page 49

15
[ 766-11-0 ]
[ 96797-15-8 ]
[ 790262-66-7 ]

Yield	Reaction Conditions	Operation in experiment
69%		A. 2-fluoro-5- (l-trityl-lH-imidazol-4-yl)-pyridine. To a solution of 4- IODO-1-TRITYL-1H-IMIDAZOLE (10.0 g, 23 mmoles) in THF (100 ml) at room temperature was added ethylmagnesium bromide (28 ml, 27.5 mmoles) under dry conditions. After stirring for 90 minutes, zinc chloride (3.8 g, 27.5 mmoles) was added to the reaction mixture. After stirring for another 90 minutes, tetrakis (triphenylphosphine) palladium (2.6 g, 2.3 mmoles) and 5-bromo-2- fluoropyridine (5.0 g, 27.5 mmoles) were added to the reaction mixture. Following that, the reaction mixture was heated in a 70C oil bath overnight. Upon cooling, the reaction was diluted with dichloromethane and washed with an EDTA buffer (at approximate pH 9) (2x 300 ml), NACI (sat. ) (300 ml), dried over sodium sulfate, filtered, and concentrated. The crude product was purified by flash 40 chromatography using an initial solvent gradient of 99.5% DCM, 0.5% MeOH, and 0. 1% TEA (1 L), then a solvent gradient of 99% DCM, 1% MeOH, and 0. 1% TEA (1 L) to yield 2-FLUORO-5- (1-TRITYL-LH-IMIDAZOL-4-YL)-PYRIDINE (6.4g, 69%). MH (406)
69%		To a solution of 4-IODO-1-TRITYL- 1H-imidazole (10.0 g, 23 mmoles) in THF (100 ml) at room temperature was added ethylmagnesium bromide (28 ml, 27.5 mmoles) under dry conditions. After stirring for 90 minutes, zinc chloride (3.8 g, 27.5 mmoles) was added to the reaction mixture. After stirring for another 90 minutes, tetrakis (triphenylphosphine) palladium (2.6 g, 2.3 mmoles) and 5-bromo-2-fluoropyridine (5.0 g, 27.5 mmoles) were added to the reaction mixture. Following that, the reaction mixture was heated in a 70C oil bath overnight. Upon cooling, the reaction was diluted with dichloromethane and washed with an EDTA buffer (at approximate pH 9) (2x 300 ml), NaCl (sat. ) (300 ml), dried over sodium sulfate, filtered, and concentrated. The crude product was purified by flash 40 chromatography using an initial solvent gradient of 99.5% DCM, 0.5% MEOH, and 0.1% TEA (1 L), then a solvent gradient of 99% DCM, 1% MEOH, and 0.1% TEA (1 L) to yield 2-FLUORO-5- (L-TRITYL-LH-IMIDAZOL-4-YL)-PYRIDINE (6.4g, 69%). MH+ (406)
		To a solution of 4-IODO-1-TRITYL-LH-IMIDAZOLE (1 eq) in THF at room temperature was added ethylmagnesium bromide (1.2 eq) under dry conditions. After stirring for 90 minutes, zinc chloride (1.2 eq) was added to the reaction mixture. After stirring for another 90 minutes, tetrakis (triphenylphosphine) palladium (10%) and 5- bromo-2-fluoropyridine (1.2 eq) were added to the reaction mixture. Subsequent reaction conditions and work up are as described previously, in Example 73 to afford the solid 2-FLUORO-5- (LH-IMIDAZOL-4-YL)-PYRIDINE (46%). MH+ (164)

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 1730 - 1743
[2]Patent: WO2004/96822,2004,A2 .Location in patent: Page 264; 265
[3]Patent: WO2004/96823,2004,A2 .Location in patent: Page 47
[4]Patent: WO2004/96822,2004,A2 .Location in patent: Page 241; 242

16
[ 96797-15-8 ]
[ 14001-66-2 ]
2-methoxy-5-(1-trityl-1H-imidazol-4-yl)-pyrimidine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 1730 - 1743

17
[ 2459-07-6 ]
[ 96797-15-8 ]
bis(1-trityl-4-imidazolyl)(2-pyridyl)carbinol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	Stage #1: N-trityl-4⁽⁵⁾-iodoimidazole With ethylmagnesium bromide In diethyl ether; dichloromethane at 20℃; for 2h; Stage #2: methyl pyridine-2-carboxylate In diethyl ether; dichloromethane at 20℃; Further stages.;

Reference： [1]Collman, James P.; Zhong, Min; Wang, Zhong [Organic Letters, 1999, vol. 1, # 6, p. 949 - 951]

18
[ 62366-53-4 ]
[ 96797-15-8 ]
bis(1-trityl-4-imidazolyl)(1-methylimidazol-2-yl)carbinol [ No CAS ]

Reference： [1]Organic Letters,1999,vol. 1,p. 949 - 951

19
[ 96797-15-8 ]
[ 154312-79-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: EtMgBr / CH₂Cl₂ 1.2: 82 percent / CH₂Cl₂ / 20 °C 2.1: NaNH₂ / tetrahydrofuran 2.2: 92 percent / tetrahydrofuran / 20 °C
	Multi-step reaction with 2 steps 1.1: EtMgBr / CH₂Cl₂; diethyl ether / 0.5 h / 20 °C 1.2: 82 percent / CH₂Cl₂; diethyl ether / 0.5 h / 20 °C 2.1: NaNH₂ / tetrahydrofuran / Heating

Reference： [1]Bertinaria, Massimo [Il Farmaco, 2003, vol. 58, # 3, p. 279 - 283]
[2]Bertinaria, Massimo; Di Stilo, Antonella; Tosco, Paolo; Sorba, Giovanni; Poli, Enzo; Pozzoli, Cristina; Coruzzi, Gabriella; Fruttero, Roberta; Gasco, Alberto [Bioorganic and Medicinal Chemistry, 2003, vol. 11, # 7, p. 1197 - 1205]

20
[ 925-90-6 ]
[ 96797-15-8 ]
[ 101048-76-4 ]
[ 222978-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	SiO2; In dichloromethane;	Step B Preparation of 2-fluoro-4-[hydroxy-(1-trityl-1H- imidazol-4-yl)-methyl]-benzonitrile To a solution of 4-iodo-1-trityl-1H-imidazole (5.00 g, 11.5 mmol) in anhydrous CH2Cl2 (30 mL) was added a 3.0M solution of ethylmagnesium bromide (6.58 mL, 19.7 mmol) with stirring under Ar. After 3 h, the reaction mixture was cooled to -78 C. and a solution of <strong>[101048-76-4]2-fluoro-4-formyl-benzonitrile</strong> (1.70 g, 11.5 mmol) dissolved in CH2Cl2 (20 mL) was added dropwise. The reaction was allowed to warm to RT over 2 h, quenched with saturated NH4Cl solution, diluted with satd. NaHCO3 solution to pH=8.5, and extracted with CH2Cl2 (3*). The combined organic layers were dried (MgSO4), concentrated and purified using SiO2 chromatography (0-1% MeOH/CH2Cl2) to yield the title compound.
	SiO2; In dichloromethane;	Step B Preparation of 2-fluoro-4-[hydroxy-(1-trityl-1H-imidazol-4-yl)-methyl]-benzonitrile To a solution of 4-iodo-1-trityl-1H-imidazole (5.00 g, 11.5 mmol) in anhydrous CH2Cl2 (30 mL) was added a 3.0M solution of ethylmagnesium bromide (6.58 mL, 19.7 mmol) with stirring under Ar. After 3 h, the reaction mixture was cooled to -78 C. and a solution of <strong>[101048-76-4]2-fluoro-4-formyl-benzonitrile</strong> (as described in Step A above) (1.70 g, 11.5 mmol) dissolved in CH2Cl2 (20 mL) was added dropwise. The reaction was allowed to warm to room temperature over 2 h, quenched with saturated NH4Cl solution, diluted with satd. NaHCO3 solution to pH=8.5, and extracted with CH2Cl2 (3*). The combined organic layers were dried (MgSO4), concentrated and purified using SiO2 chromatography (0-1% MeOH/CH2Cl2) to yield the title compound.
	SiO2; In dichloromethane;	Step B Preparation of 2-Fluoro-4-[hydroxy-(1-trityl-1H-imidazol-4-yl)-methyl]-benzonitrile To a solution of 4-iodo-1-trityl-1H-imidazole (5.00 g, 11.5 mmol) in anhydrous CH2Cl2 (30 mL) was added a 3.0M solution of ethylmagnesium bromide (6.58 mL, 19.7 mmol) with stirring under Ar. After 3 h, the reaction mixture was cooled to -78 C. and a solution of <strong>[101048-76-4]2-fluoro-4-formyl-benzonitrile</strong> (1.70 g, 11.5 mmol) dissolved in CH2Cl2 (20 mL) was added dropwise. The reaction was allowed to warm to RT over 2 h, quenched with saturated NH4Cl solution, diluted with satd. NaHCO3 solution to pH=8.5, and extracted with CH2Cl2 (3*). The combined organic layers were dried (MgSO4), concentrated and purified using SiO2 chromatography (0-1% MeOH/CH2Cl2) to yield the title compound.

	SiO2; In dichloromethane;	Step B Preparation of 2-fluoro-4-[hydroxy-(1-trityl-1H-imidazol-4-yl)-methyl]-benzonitrile To a solution of 4-iodo-1-trityl-1H-imidazole (5.00 g, 11.5 mmol) in anhydrous CH2Cl2 (30 mL) was added a 3.0M solution of ethylmagnesium bromide (6.58 mL, 19.7 mmol) with stirring under Ar. After 3 h, the reaction mixture was cooled to -78 C. and a solution of <strong>[101048-76-4]2-fluoro-4-formyl-benzonitrile</strong> (as described in Step A above) (1.70g, 11.5 mmol) dissolved in CH2Cl2 (20 mL) was added dropwise. The reaction was allowed to warm to room temperature over 2 h, quenched with saturated NH4Cl solution, diluted with satd. NaHCO3 solution to pH=8.5, and extracted with CH2Cl2 (3*). The combined organic layers were dried (MgSO4), concentrated and purified using SiO2 chromatography (0-1% MeOH/CH2Cl2) to yield the title compound.
	SiO2; In dichloromethane;	Step B Preparation of 2-fluoro-4-[hydroxy-(1-trityl-1H-imidazol-4-yl)-methyl]-benzonitrile To a solution of 4-iodo-1-trityl-1H-imidazole (5.00 g, 11.5 mmol) in anhydrous CH2Cl2 (30 mL) was added a 3.0M solution of ethylmagnesium bromide (6.58 mL, 19.7 mmol) with stirring under Ar. After 3 h, the reaction mixture was cooled to -78 C. and a solution of <strong>[101048-76-4]2-fluoro-4-formyl-benzonitrile</strong> (as described in Step A above) (1.70 g, 11.5 mmol) dissolved in CH2Cl2 (20 mL) was added dropwise. The reaction was allowed to warm to RT over 2 h, quenched with saturated NH4Cl solution, diluted with satd. NaHCO3 solution to pH=8.5, and extracted with CH2Cl2 (3*). The combined organic layers were dried (MgSO4), concentrated and purified using SiO2 chromatography (0-1% MeOH/CH2Cl2) to yield the title compound.

Reference： [1]Patent: US2003/220241,2003,A1
[2]Patent: US2003/220241,2003,A1
[3]Patent: US6297239,2001,B1
[4]Patent: US6284755,2001,B1
[5]Patent: US6284755,2001,B1

21
[ 56423-63-3 ]
[ 14221-01-3 ]
[ 925-90-6 ]
[ 96797-15-8 ]
2-(1H-Imidazol-4-yl)-pyrazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Zinc chloride; In tetrahydrofuran;	EXAMPLE 92(f) Synthesis of 2-(1H-Imidazol-4-yl)-pyrazine To a solution of 4-Iodo-1-trityl-1H-imidazole (1 eq) in THF at room temperature was added ethylmagnesium bromide (1.2 eq) under dry conditions. After stirring for 90 minutes, zinc chloride (1.2 eq) was added to the reaction mixture. After stirring for another 90 minutes, tetrakis(triphenylphosphine) palladium (10%) and 5-<strong>[56423-63-3]bromopyrazine</strong> (1.3 eq) were added to the reaction mixture. Subsequent reaction conditions and work up are as described previously in Example 73, the resulting solid 2-(1H-Imidazol-4-yl)-pyrazine (37%) was collected by filtration. MH+(147)

Reference： [1]Patent: US2003/125266,2003,A1

22
[ 71759-89-2 ]
[ 60-29-7 ]
[ 76-83-5 ]
[ 96797-15-8 ]

Yield	Reaction Conditions	Operation in experiment
92%	In N,N-dimethyl-formamide;	EXAMPLE 90 Synthesis of 4-Iodo-1-trityl-1H-imidazole To a solution of <strong>[71759-89-2]4-iodoimidazole</strong> (1 eq) in DMF at room temperature was added triphenylmethyl chloride (1.2 eq). After stirring at room temperature for 24 hours, the solution was poured into ice water and left stirring for 30 minutes. The solid was filtered and pumped on for several hours to yield the crude compound. Ethyl ether was added to the crude compound and the solution was filtered to yield 4-Iodo-1-trityl-1H-imidazole (92%) as a white solid. MH+(437).

Reference： [1]Patent: US2003/125266,2003,A1

23
aq. NH₄Cl [ No CAS ]
[ 96797-15-8 ]
[ 101048-76-4 ]
[ 222978-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	With MeMgBr; In tetrahydrofuran; diethyl ether; dichloromethane;	Step D: Preparation of (4-cyano-3-fluorophenyl)[1-(triphenylmethyl)imidazol-4-yl]methanol To a solution of 4-iodo-1-(triphenylmethyl)imidazole (2.93 g, 6.71 mmol) in dry CH2Cl2 (30 mL), under argon, was added MeMgBr (2.35 mL of a 3.0 M solution in Et2O, 7.05 mmol), dropwise. The resulting solution was stirred at ambient temperature for 1 hr, then transferred dropwise into a stirred solution of <strong>[101048-76-4]4-cyano-3-fluorobenzaldehyde</strong> from Step C (1.00 g, 6.71 mmol) in dry THF (30 mL), under argon, at -78 C. After 30 min, the reaction mixture was quenched with sat. aq. NH4Cl (50 mL) and extracted with CH2Cl2 (3*50 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was triturated with EtOAc to yield the desired aldehyde as a white solid of sufficient purity for use in the next step.

Reference： [1]Patent: US6358985,2002,B1

24
ammonium chloride [ No CAS ]
[ 96797-15-8 ]
[ 101048-76-4 ]
[ 222978-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	With MeMgBr; In tetrahydrofuran; diethyl ether; dichloromethane;	Step A (4-Cyano-3-fluorophenyl)[1-(triphenylmethyl)imidazol-4-yl]methanol To a solution of 4-iodo-1-(triphenylmethyl)imidazole (2.93 g, 6.71 mmol) in dry CH2Cl2 (30 mL), under argon, was added MeMgBr (2.35 mL of a 3.0M solution in Et2O, 7.05 mmol), dropwise. The resulting solution was stirred at ambient temperature for 1 hour, then transferred dropwise into a stirred solution of <strong>[101048-76-4]4-cyano-3-fluorobenzaldehyde</strong>, as described in Example 11, Step B, (1.00 g, 6.71 mmol) in dry THF (30 mL), under argon, at -78 C. After 30 min, the reaction mixture was quenched with saturated aqueous NH4Cl (50 mL) and extracted with CH2Cl2 (3*50 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was triturated with EtOAc to yield the desired alcohol as a white solid.

Reference： [1]Patent: US6441017,2002,B1

25
[ 32896-02-9 ]
[ 925-90-6 ]
[ 96797-15-8 ]
[ 189745-63-9 ]

Yield	Reaction Conditions	Operation in experiment
5.3 g (69%)	With ammonium chloride In diethyl ether; dichloromethane; chloroform	8 4-[-(3,4-Dibromothien-2-yl)ethyl]-1H Fumarate STR47 To a solution of 4-iodo-1-trityl imidazole (5.8 g, 0.0133 mol) in 75 mL of dry dichloromethane under nitrogen was added dropwise a solution of ethyl magnesium bromide in diethyl ether (4.4 mL, 3.0M). When addition was complete, the reaction mixture was stirred for 45 min at 25° C. TLC analysis indicated that some starting material remained so an additional 1.0 mL of Grignard reagent was added. After 1 h of stirring, TLC analysis indicated that the starting material was gone, and 3,4-dibromothiophene-2-carboxaldehyde, A8, (3.6 g, 0.0133 mol) was added as a solution in dichloromethane. After overnight stirring at ambient temperature, the reaction was quenched with saturated ammonium chloride solution. The layers were separated, and the aqueous layer was extracted again with dichloromethane. The organic layers were combined, dried (Na2 SO4), and concentrated to provide an off-white solid. This material was recrystallized from ethyl acetate with a small amount of chloroform added to aid in dissolution. Filtration afforded 5.3 g (69%) of 4-(3,4-dibromothien-2-yl)methanol-1-trityl-imidazole, B8, as a white solid.

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - US5621113, 1997, A

26
[ 765-77-5 ]
[ 96797-15-8 ]
[ 197723-96-9 ]

Yield	Reaction Conditions	Operation in experiment
	With ethylmagnesium bromide In diethyl ether; dichloromethane; ethyl acetate	2 4-[(4-Methylthien-3-yl)methyl]-1H-imidazole Fumarate STR37 To a solution of N-trityl-4-iodo-imidazole (11.8 g, 27 mmol) in dry CH2 Cl2 (75 mL) was added EtMgBr (10.0 mL, 3.0M in Et2 O), and the solution was stirred for 3 hrs. Then a solution of 4-methylthiophene-3-carboxaldehyde (3.3 g, 27 mmol) in CH2 Cl2 (25 mL) was added. The reaction mixture was stirred at room temperature overnight and then was quenched with aqueous NH4 Cl. The mixture was transferred to a separatory funnel, and the aqueous layer was extracted with a second portion of CH2 Cl2. The combined extracts were washed with a small portion of water, dried (Na2 SO4), and filtered. The solvent was evaporated in vacuo to give a thick syrup which was triturated with Et2 O to give a solid which was recrystallized with charcoal treatment from EtOAc to give (4-methylthien-3-yl)-1-trityl-imidazol-4-yl-methanol, B2. 1 H NMR (CDCl3) supported the assigned structure. STR39

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - US5750720, 1998, A

27
[ 26421-44-3 ]
[ 96797-15-8 ]
(2,5-dimethylthien-3-yl)-1-trityl-imidazol-4-yl-methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With ethylmagnesium bromide; In diethyl ether; dichloromethane;	EXAMPLE 5 4-[(2,5-dimethylthien-3-yl)methyl]-1H-imidazole Fumarate STR45 To a solution of N-trityl-4-iodo-imidazole (11.8 g, 27 mmol) in dry CH2 Cl2 (200 mL) was added EtMgBr (11.0 mL, 3.0M in Et2 O). After complete halogen-metal exchange this solution was cannulated into a solution of <strong>[26421-44-3]2,5-dimethylthiophene-3-carboxaldehyde</strong> (3.5 g, 25 mmol) in 50 mL of CH2 Cl2. The reaction mixture was stirred at room temperature for 1 hr and then quenched with aqueous NH4 Cl. The mixture was transferred to a separatory funnel and the aqueous layer was extracted with a second portion of CH2 Cl2. The combined extracts were dried (MgSO4) and filtered. The solvent was evaporated in vacuo to give a thick syrup which was triturated with Et2 O to give a solid which was recrystallized from acetone to give (2,5-dimethylthien-3-yl)-1-trityl-imidazol-4-yl-methanol, A5. 1 H NMR (CDCl3) supported the assigned structure. STR46

Reference： [1]Patent: US5750720,1998,A

28
NiCl₂ (PPh₃)2 [ No CAS ]
[ 557-91-5 ]
[ 96797-15-8 ]
[ 222978-03-2 ]
[ 275807-74-4 ]

Yield	Reaction Conditions	Operation in experiment
	SiO2; In tetrahydrofuran;	Step A Preparation of 2-fluoro-4-(1-trityl-1H-imidazol-4-ylmethyl)-benzonitrile Zinc (0.301 g, 4.63 mmol) and dibromoethane (0.040 mL, 0.463 mmol) were stirred in anhydrous THF (2 mL) under Ar for 1.5 h. A solution of <strong>[222978-03-2]4-bromomethyl-2-fluoro-benzonitrile</strong> (as described in Example 1, Step D) (0.546 g, 2.55 mmol) in anhydrous THF (1 mL) was added dropwise and stirred for 1 h. A mixture of 4-iodo-1-trityl-1H-imidazole (0.808 g, 1.85 mmol) and NiCl2 (PPh3)2 (0.120 g, 0.183 mmol) were added together to the reaction. After stirring overnight under Ar, the reaction was quenched with NH4Cl (9 mL), stirred for 2 h, extracted with CH2Cl2 (3*), dried (MgSO4), concentrated and purified using SiO2 chromatography (0.5% MeOH/CH2Cl2 w/NH4OH) to give the title compound.

Reference： [1]Patent: US6284755,2001,B1

29
[ 96797-15-8 ]
[ 105942-09-4 ]
[ 928136-92-9 ]

Yield	Reaction Conditions	Operation in experiment
		3-Fluoro-4-(5-iodo-imidazol-1-ylmethyl)benzonitrile A mixture of 4-iodo-1-trityl-1H-imidazole (17.1 g, 39.2 mmol) and <strong>[105942-09-4]4-bromomethyl-3-fluorobenzonitrile</strong> (9.65 g, 45.08 mmol) in 150 mL of dry actetonitrile is stirred at room temperature for 7 days. After concentration, the residue is mixed with methanol, and heated to reflux for 1.5 h. The solvent is subsequently removed and the residue is treated with 1M HCl (300 mL). The resulting suspension is filtered and the washed with HCl (1M). The combined solution is adjusted to PH 9-10 by saturated NaHCO3 solution. The resulting precipitation is collected by filtration, dried in vacuum oven. MS (ESI) m/z (M+H) 328.1.

Reference： [1]Patent: US2007/49616,2007,A1 .Location in patent: Page/Page column 44

30
[ 5779-93-1 ]
[ 96797-15-8 ]
[ 176721-01-0 ]

Yield	Reaction Conditions	Operation in experiment
84%		Example 1 (step a); Preparation of (2,3-Dimethylphenyl)-(3-trityl-3H-imidazol-4-yl)methanol A solution of isopropylmagnesium bromide in tetrahydrofuran (48 mL, 0.046 mol) was added to a stirred solution of 4-iodo-1-trityl-1 H-imidazole (19.0 g, 0.046 mol) in dichloromethane (180 mL) at 10 to 15°C. The reaction mixture was allowed to warm to the ambient temperature and was stirred at ambient temperature for 1 hour. The reaction mixture was then cooled to 10-15°C, at which point a solution of <strong>[5779-93-1]2,3-dimethylbenzaldehyde</strong> (6.2 mL, 0.046 mol) in dichloromethane (10 mL) was added, while not exceeding 20 to 25°C. After additional stirring for 1 hour at ambient temperature a 10percent aqueous ammonium chloride solution (200 mL) was added to the reaction mixture. The organic layer was separated and washed with an aqueous sodium chloride solution (150 mL), thereafter the organic layer was concentrated to a volume of 40 mL. A precipitate of (2,3-dimethylphenyl)-(3-trityl-3H-imidazol-4-yl)methanol was obtained upon cooling the distillation residue to 4°C and it was separated by filtration, then washed with dichloromethane (50 mL). The intermediate (2,3-dimethylphenyl)-(3-trityl-3H-imidazol-4-yl)methanol was dried at ambient temperature. The yield was 17.4 g (84 percent) of a white or off-white powder, having a melting temperature of 203.0 to 207.0°C.

Reference： [1]Patent: EP1918282,2008,A1 .Location in patent: Page/Page column 5

31
[ 1049633-96-6 ]
[ 925-90-6 ]
[ 96797-15-8 ]
[ 1049634-03-8 ]

Yield	Reaction Conditions	Operation in experiment
72%		Step 11C 62ATo a solution of 4-iodo-trityl-imidazole (6.77 g, 15.5 mmol) in DCM (100 ml_) was added EtMgBr (3.0M in Et2O, 4.96 mL, 14.9 mmol) slowly at -200C, stirred at - 200C for 30 min. A solution of 1C (2.8 g, 13.5 mol) in DCM (20 mL) was added very slowly. The mixture was stirred at RT for 1 h, quenched with saturated NH4CI, diluted with DCM. The DCM layer was washed with brine, dried and concentrated. Flash chromatography (EtOAc/Hexanes, 1 :2 then 10:1 ) afforded 62A (5.0 g, 72%).

Reference： [1]Patent: WO2008/100459,2008,A1 .Location in patent: Page/Page column 81

32
[ 500-22-1 ]
[ 96797-15-8 ]
[ 1080643-08-8 ]

Yield	Reaction Conditions	Operation in experiment
82%		A mixture of 4-iodo-l-tritylimidazole (commercially available) (10.1 g, 23.3 mmol) in dichloromethane ( 100 mL) at -10 0C was treated with ethyl magnesium bromide (7.76 mL, 23.3 mmol, 3M in ether) and allowed to react for 45 minutes. A solution of 3-picolinaldehyde, (intermediate 7) (2 g, 18.69 mmol) in dichloromethane was added via syringe at -10 0C and stirred for 16 hours at room temperature. The mixture was quenched with water (50 mL) and a sat. solution of ammonium chloride (50 mL). The residue was isolated in a typical aqueous workup gave pyridin-3-yl( l-trityl-lH-imidazol- 5-yl)methanol, (intermediate 8) as a solid, 6.48 g (82%).

Reference： [1]Patent: WO2008/141312,2008,A1 .Location in patent: Page/Page column 12

33
[ 96797-15-8 ]
[ 85070-48-0 ]
(3-chloro-2-fluorophenyl)(1-trityl-1H-imidazol-4-yl) methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78.7%		A solution of 4-iodo-l-tritylimidazole (commercially available, 5.1 g, 1 1.8 mmol) in dichloromethane (40 ?iL) at -10 0C was treated with ethyl magnesium bromide (3.9 mL, 1 1.8 mmol, 3M in ether) and allowed to react for 45 m. A solution of <strong>[85070-48-0]3-chloro-2-fluoro-benzaldehyde</strong>, (Intermediate 1) (1.5 g, 9.4 mmol) in dichloromethane was added via syringe at -10 0C and stirred for 16 hours at room temperature. The mixture was quenched with water (50 mL) and a saturated solution of ammonium chloride (50 mL). The residue was isolated in a typical aqueous workup and purified by MPLC with 3 to 5 % MeOHiCH2Cl2 to give (3-chloro-2-fluorophenyl)(l-trityl-l H-imidazol-4-yl) methanol, (Intermediate 2) as a solid, (3.5 g 78

Reference： [1]Patent: WO2008/141312,2008,A1 .Location in patent: Page/Page column 10

34
[ 38707-70-9 ]
[ 96797-15-8 ]
[ 1087181-43-8 ]

Yield	Reaction Conditions	Operation in experiment
82.7%		58] Intermediate 14 301[59] A solution of 4-iodo-l-tritylimidazole (commercially available) 5.2 g, 11.94 mmol) in dichloromethane (80 mL) at -10 0C was treated with ethyl magnesium bromide (3.98 mL, 11.94 mmol, 3M in ether) and allowed to react for 45 m. A solution of <strong>[38707-70-9]quinoline-8-carbaldehyde</strong>, (Intermediate 11) (1.5 g, 9.55 mmol) in dichloromethane was added via syringe at -10 0C and stirred for 16 h at room temperature. The mixture was quenched with water (50 mL) and a sat. solution of ammonium chloride (50 mL) and subjected to an aqueous work-up. The residue was purified by chromatography on silica gel with 3% NH3-MeOH: CH2Cl2 to give to give quinolin-8-yl(l-trityl-lH-imidazol-5- yl)methanol, (Intermediate 12) as a solid, (3.7 g 82.7%).

Reference： [1]Patent: WO2008/147786,2008,A1 .Location in patent: Page/Page column 12

35
[ 96797-15-8 ]
[ 32779-36-5 ]
[ 885369-67-5 ]

Yield	Reaction Conditions	Operation in experiment
67%		Step 1: Preparation of 2-chloro-5-(1-trityl-H-imidazol-4-yl)pydimidine A 3M solution of ethyl magnesium bromide in diethylether (12.66 mmol) was added to a solution of 4-iodo-1-trityl-1H-imidazole (10.55 mmol) in freshly distilled dry tetrahydrofuran (46.0 mL) in a three necked round bottom flask at room temperature. The reaction mixture was stirred for about 90 minutes and then a 1M solution of zinc chloride (12.66 mmol) was added at room temperature. The solution was stirred for about 90 minutes and then degassed for about 20.0 minutes. Palladium triphenylphosphine (0.61 g, 0.527 mmol) and 5-bromo-2-chloro pyrimidine (11.6 mmol) were added and the reaction mixture was stirred for about 12-14 hrs at about 70 C. The reaction mixture was cooled, diluted with dichloromethane (100.0 mL), washed with aqueous solution of ethylenediaminetetraacetic acid (pH 9), brine, dried over anhydrous sodium sulfate, filtered and concentrated to yield a solid, which was purified by column using ethyl acetate-hexane as eluent to yield the title compound. Yield: 3.0 g (67%).
		Ethyl magnesium bromide (1M) in tetrahydrofuran (12.66 mL, 12.66 mmol) was added to the solution of 4-iodo-1-trityl-1H-imidazole (4.6 g, 10.55 mmol) in freshly distilled dry tetrahydrofuran (46.0 mL) at an ambient temperature and the reaction mixture was stirred for about 90 minutes. Zinc chloride (1M) (12.66 mL, 12.66 mmol) was added at an ambient temperature and was stirred for another about 90 minutes. The reaction mixture was degassed for about 20 minutes. Tetrakis(triphenylphosphine) palladium (0.61 g, 0.527 mmol) and 5-bromo-2-chloro pyrimidine (2.24 g, 11.6 mmol) was added and the reaction mixture was stirred for about 12-14 hours at about 70 C. The reaction mixture was cooled and diluted with dichloromethane, washed with aqueous solution of EDTA (PH=9), brine, dried over anhydrous sodium sulphate, filtered and concentrated to form the solid, which was purified by column chromatography using ethyl acetate-hexane as eluents. Yield: 3.0 g
		Ethyl magnesium bromide (IM) in tetrahydrofuran (12.66 mL, 12.66 mmol) was added to the solution of 4-iodo-l-trityl-lH-imidazole (4.6g, 10.55 mmol) in freshly distilled dry tetrahydrofuran (46.0 mL) at an ambient temperature and the reaction mixture was stirred for about 90 minutes. Zinc chloride (IM) (12.66 mL, 12.66 mmol) was added at an ambient temperature and was stirred for another about 90 minutes. The reaction mixture was degassed for about 20 minutes. Tetrakis(triphenylphosphine) palladium (0.61g, 0.527 mmol) and 5-bromo-2-chloro pyrimidine (2.24 g,l 1.6 mmol) was added and the reaction mixture was stirred for about 12-14 hours at about 700C. The reaction mixture was cooled and diluted with dichloromethane, washed with aqueous solution of EDTA (PH=9), brine, dried over anhydrous sodium sulphate, filtered and concentrated to form the solid, which was purified by column chromatography using ethyl acetate-hexane as eluents. Yield: 3.0g

Reference： [1]Patent: US2009/170790,2009,A1 .Location in patent: Page/Page column 24
[2]Patent: US2009/130225,2009,A1 .Location in patent: Page/Page column 17
[3]Patent: WO2007/60618,2007,A2 .Location in patent: Page/Page column 24; 31

36
[ 96797-15-8 ]
[ 95092-10-7 ]
[ 1169826-20-3 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: N-trityl-4⁽⁵⁾-iodoimidazole With ethylmagnesium bromide In diethyl ether; dichloromethane at -10℃; for 0.75h; Stage #2: N-methoxy-N-methyl-2-phenylacetamide In diethyl ether; dichloromethane at -10 - 20℃; for 16h;	D.D A solution of 4-iodo-l-tritylimidazole (commercially available, 5.08 g, 13.7 mmol) in dichloromethane (100 mL) at -10° C. was treated with ethylmagnesium bromide (4.5 mL, 13.7 mmol, 3M in ether) and allowed to react for 45 m. A solution of N-methoxy-N-methyl-2-phenylacetamide, (Intermediate 13) (2.0 g, 11.2 mmol) in dichloromethane was added via syringe at -10° C. and stirred for 16 hours at room temperature. The mixture was quenched with water (50 mL) and a saturated solution of ammonium chloride (50 mL). The residue was isolated in a typical aqueous workup and purified by MPLC with 3 to 5% MeOH:CH2Cl2 to give 2-phenyl-l-(1-trityl-1H-imidazol-4-yl)ethanone, (Intermediate 14) as a solid, (4.65 g).

Reference： [1]Current Patent Assignee: ABBVIE INC - US2009/176843, 2009, A1 Location in patent: Page/Page column 9

37
[ 207853-70-1 ]
[ 96797-15-8 ]
[ 1173089-32-1 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: N-trityl-4⁽⁵⁾-iodoimidazole With ethylmagnesium bromide In diethyl ether; dichloromethane at -10℃; for 0.75h; Stage #2: (2-fluoro-3-(trifluoromethyl)phenyl)(phenyl)methanone In diethyl ether; dichloromethane at -10 - 20℃; for 16h; Stage #3: With triethylsilane; water; ammonium chloride; trifluoroacetic acid more than 3 stages;	C Example C; Method C: Procedure for the preparation of 5-((2-fluoro-3- (trifluoromethyl)phenyl) (phenyl) methyl)-1 H-imidazole; A mixture of 4-iodo-1 -tritylimidazolθ (commercially available) (3.2 g, 7.4 mmol) in dichloromethane (40 mL) at -10 0C was treated with ethyl magnesium bromide (2.4 mL, 7.4 mmol, 3M in ether) and allowed to react for 45 m. A solution of (2-fluoro-3-(trifluoromethyl)phenyl)(phenyl)methanone, (Intermediate 7) (1 g, 3.7 mmol) in dichloromethane was added via syringe at - 10 0C and stirred for 16 h at rt. The mixture was quenched with water (50 mL) and a saturated solution of ammonium chloride (20 mL). The residue was isolated in a typical aqueous workup gave (2-fluoro-3- (trifluoromethyl)phenyl)(phenyl)(1-trityl-1 H-imidazol-5-yl)mβthanol, (Intermediate 8), 2.02 g (94% crude).[0092] (2-fluoro-3-(trifluoromethyl)phenyl)(phenyl)(1 -trityl-1 H-imidazol-5- yl)methanol, (Intermediate 8) (2.02 g, 3.49 mmol) in dichloromethane (30 mL) was reacted with TFA: trifluoroacetic acid (5.3 mL, 68 mmol)) and triethylsilane (TES) (2.8 mL, 17 mmol) at room temperature for 24 hours. The mixture was evaporated under reduced pressure and quenched with solid NaHCO3. This material was subjected to an aqueous work-up and the residue was purified by chromatography on silica gel with 5% NH3-MeOHiCH2CI2 to yield 5-((2-fluoro- 3-(trifluoromethyl)phenyl)(phenyl)methyl)-1 H-imidazole 700 mg (62%). 1HNMR (CD3OD, 300MHz): 67.54 (s, 1 H), 7.52-7.26 (m, 3H), 7.18-7.11 (m, 4H)1 6.66 (S1 1 H), 5.84 (S1 1 H), 5.49 (S, 1 H).

Reference： [1]Current Patent Assignee: ABBVIE INC - WO2009/91735, 2009, A1 Location in patent: Page/Page column 23

38
[ 750598-19-7 ]
[ 96797-15-8 ]
[ 1172128-06-1 ]

Yield	Reaction Conditions	Operation in experiment
54%		S-Fluoro^-Cl^.S-tri-O-benzoyl-yS-D-ribofuranosyO^^l-trityl-lir- imidazoI-4-yl)-7H-pyrrolo[2,3-<flpyrimidine (7h). Ethylmagnesium bromide (IM sol. in THF, 1.84 mL, 1.84 mM) is added to an argon purged solution of 4- iodo-1-trityl-lH-imidazole (696 mg, 1.6 mM) in dry THF (6 mL) and the resulting solution is stirred for 10 min at ambient temperature, followed by the addition of solution of ZnCl2 (IM sol. in THF, 3.2 mL, 3.2 mM). The mixture is stirred for 2 h at RT and the resulting thick white slurry is transferred to an argon purged flask with 6-chloro-7-fluorodeazapurine riboside 6 (493 mg, 0.8 mM) and Pd(PPh3)4 (46 mg, 0.04 mM) and stirred at 95C for 12 h. The mixture is diluted with chloroform (20 mL) and washed with aqueous EDTA (sat., 20 mL). Aqueous layer is re-extracted with chloroform (2 x 5 mL). Collected organic extracts are dried over MgSO4, evaporated and chromatographed on silica(hexanes-AcOEt, 2:1) affording product 7h (386 mg, 54%) as orange foam. 1H NMR (600 MHz, CDCl3): 4.67 (dd, IH, Jgem = 12.2, J5 ^4- = 3.9, H-5'b); 4.77 (ddd, IH, J4',5' = 3.9, 3.2, J4-,3- = 3.7, H-4'); 4.84 (dd, IH, Jgem = 12.2, J5-M< = 3.2, H-5'a); 6.04 (dd, IH, J3-? = 5.8, J3- A- = 3.7, H-3'); 6.07 (t, IH, J2-, y = J2-? = 5.8, H-2'); 6.84 (dd, IH, J1-? = 5.8, JH,F = 1.0, H-I '); 7.13 (bs, IH, H-6); 7.16-7.20 (m, 6H, H-o-Tr); 7.32-7.38 (m, HH, H-m,p-Tr and H-°i-Bz); 7.41 and 7.48 (2 x m, 2 x 2H, H-W-Bz); 7.53, 7.58 and 7.59 (3 x m, 3 x IH, H-^-Bz); 7.69 (bs, IH, H-2-imidazole); 7.84 (d, IH, J5;2 = 1.3, H-5-imidazole); 7.90, 8.01 and 8.12 (3 x m, 3 x 2H, H-o-Bz); 8.83 (s, IH, H-2). 13C NMR (151 MHz, CDCl3): 63.81 (CH2-5'); 71.46 (CH-3'); 73.71 (CH-2'); 76.42 (C-Tr); 80.36 (CH-4'); 85.25(CH-I '); 104.39 (d, JC,F = 16, C-4a); 108.13 (b, CH-6); 125.70 (d, JC)F = 16, CH- 5-imidazole); 128.28, 128.46, 128.53 (CH-°i-Bz and CH-w^-Tr); 128.67 (C-z- Bz); 128.70 (CH-m-Bz); 129.27 (C-z-Bz); 129.65, 129.72 and 129.81 (CH-o-Bz <n="102"/>and CH-o-Tr); 133.49 and 133.72 (CH-p-Bz); 137.17 (C-4-imidazole); 140.21 (CH-2-imidazole); 141.64 (C-z-Tr); 143.02 (d, JC,F = 251, C-5); 148.11 (C-4 and C-7a); 152.22 (CH-2); 165.09, 165.40 and 166.11 (CO). 19F NMR (470.3 MHz, CDCl3): -158.87

Reference： [1]Patent: WO2009/89804,2009,A1 .Location in patent: Page/Page column 100; 101

39
[ 96797-15-8 ]
[ 115479-39-5 ]
[ 1172127-87-5 ]

Yield	Reaction Conditions	Operation in experiment
66%		Ethylmagnesium bromide (IM sol. in THF5 2.3 mL, 2.3 mM) is added to an argon purged solution of 4-iodo-l -trity 1-1 //-imidazole (872 mg, 2 mM) in dry THF (6 mL) and the resulting solution is stirred for 10 min at ambient temperature, followed by the addition of solution OfZnCl2 (IM sol. in THF, 4 mL, 4mM). The mixture is stirred for 2 h at RT and the resulting thick white slurry is transferred to an argon purged flask with chlorodeazapurine 1 (440 mg, 1 mM) and Pd(PPh3)4 (58 mg, 0.05 mM) and stirred at 95C for 12 h. The mixture is diluted with chloroform (20 mL) and washed with aqueous EDTA (sat., 20 mL). Aqueous layer is re-extracted with chloroform (2 x 5 mL). Collected organic extracts are dried over MgSO4, evaporated and chromatographed on silica (hexanes-AcOEt, 2.5:1) affording product 2j (474 mg, 66%) as redish foam. H NMR (500 MHz, CDCl3): 0.053 and 0.056 (2 x s, 2 x 3H, CH3Si); 0.90 (s, 9H5 (CH3)3CSi); 1.39 and 1.66 (2 x bs, 2 x 3H, (CH3)2C); 3.79 (dd5 lH, Jgem = 11. l, Js%4- = 3.9, H-5'b); 3.87 (dd5 lH, Jgem = 11.1, Jw = 3.9, H-5'a); 4.32 (td, IH, J4- No. = 3.9, J4- beta- = 3.2, H-4'); 4.99 (dd, IH, J3-? = 6.4, J37T = 3.2, H-3'); 5.13 (dd, IH, J2-? = 6.4, Jx x = 3.0, H-2'); 6.45 (d, IH, Jx-? = <n="72"/>3.0, H-I '); 7.19-7.22 (m, 6H, H-o-Tr); 7.32-7.37 (m, 9H5 U-m,p-Tv); 7.38 (d, IH3 J5j6 = 3.8, H-5); 7.48 (d, IH3 J6;5 = 3.8, H-6); 7.61 (d, IH, J2;5 = 1.4, H-2- imidazole); 7.90 (d, IH, J5;2 = 1.4, H-5-imidazole); 8.75 (s, IH, H-2). 13C NMR (125.7 MHz, CDCl3): -5.48 and -5.36 (CH3Si); 18.38 (SiC(CH3)-,); 25.50 ((CHg)2C); 25.93 ((CH3)3C); 27.35 ((CHs)2C); 63.35 (CH2-S'); 75.87 (C-Tr); 80.95 (CH-3'); 84.92 (CH-2'); 85.97 (CH-4'); 89.96 (CH-I '); 103.38 (CH-5); 114.06 (C(CH3)2); 114.81 (C-4a); 123.27 (CH-5-imidazole); 126.07 (CH-6); 128.19 (CH-m,p-Ttau:y, 129.80 (CH-o-Tr); 140.17 (CH-2-imidazole); 140.51 (C-4- imidazole); 142.08 (C-z-Tr); 151.32 (CH-2); 151.83 (C-4); 151.92 (C-7a). MS FAB, mlz (rel. %): 243 (100), 434 (15), 714 (S)[MfH]. HR MS (FAB): calcd for C42H48N5O4Si [M+H] 714.3476, found 714.3447

Reference： [1]Patent: WO2009/89804,2009,A1 .Location in patent: Page/Page column 70; 71
[2]Journal of Medicinal Chemistry,2010,vol. 53,p. 460 - 470

40
[ 36953-42-1 ]
[ 96797-15-8 ]
C₂₇H₂₀ClN₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		A. 4-CHLORO-3-(LH-IMIDAZOL-4-YL)-PYRIDINE. To a solution of 4-iodo-1- trityl-lH-imidazole (13 g, 30.3 mmoles) in THF (150 ml) at room temperature was added ethylmagnesium bromide (43 ML, 33 mmoles) under dry conditions. After stirring for 90 minutes, zinc chloride (4.5 g, 33 mmoles) was added to the reaction mixture. After stirring for another 90 minutes, tetrakis (triphenylphosphine) palladium (3.5 g, 3 mmoles) and 5-bromo-2-chloropyridine (7.0 g, 36 mmoles) were added to the reaction mixture. Following that, the reaction mixture was heated in a 70C oil bath overnight. Upon cooling, the reaction was diluted with dichloromethane and washed with an EDTA buffer (at approximate pH 9) (300 ml), NaCl (sat. ) (150 ml), dried over sodium sulfate, filtered, and concentrated. To the crude material in DCM (250 ml) at room temperature was added trifluoroacetic acid (60 ml, 780 mmoles). After stirring for 90 minutes, the excess TFA and DCM were removed in vacuo. The crude product was left under high vacuum pump overnight. To the crude product was added 60 ml of 3 N HCl and the mixture was left in the sonicator for 120 minutes. Once recovered from the sonicator, the mixture was filtered and the aqueous solution was washed with diethyl ether until the organic phase was no more UV active. The aqueous solution was cooled to 0C and 30% NaOH solution was added until an approximate pH 7-8 was obtained. The obtained solid product was filtered and dried over night under high vacuum pump to yield 4-CHLORO-3-(LH-IMIDAZOL-4-YL)-PYRIDINE (3. 32 G, 61%). MH+ (180)
		To a solution of 4-iodo-1-trityl-1H- imidazole (13 g, 30.3 mmoles) in THF (150 ml) at room temperature was added ethylmagnesium bromide (43 ml, 33 mmoles) under dry conditions. After stirring for 90 minutes, zinc chloride (4.5 g, 33 mmoles) was added to the reaction mixture. After stirring for another 90 minutes, tetrakis (triphenylphosphine) palladium (3.5 g, 3 mmoles) and 5-bromo-2-chloropyridine (7.0 g, 36 mmoles) were added to the reaction mixture. Following that, the reaction mixture was heated in a 70C oil bath overnight. Upon cooling, the reaction was diluted with dichloromethane and washed with an EDTA buffer (at approximate pH 9) (300 ML), NaCl (sat. ) (150 ml), dried over sodium sulfate, filtered, and concentrated. To the crude material in DCM (250 ml) at room temperature was added trifluoroacetic acid (60 ml, 780 mmoles). After stirring for 90 minutes, the excess TFA and DCM were removed in vacuo. The crude product was left under high vacuum pump overnight. To the crude product was added 60 ml of 3N HCl and the mixture was left in the sonicator for 120 minutes. Once recovered from the sonicator, the mixture was filtered and the aqueous solution was washed with diethyl ether until the organic phase was no more UV active. The aqueous solution was cooled to 0C and 30% NaOH solution was added until an approximate pH 7-8 was obtained. The obtained solid product was filtered and dried over night under high vacuum pump to yield 4-CHLORO-3- (LH- imidazol-4-yl) -pyridine (3.32 g, 61 %). MH+ (180).

Reference： [1]Patent: WO2004/96822,2004,A2 .Location in patent: Page 272
[2]Patent: WO2004/96823,2004,A2 .Location in patent: Page 54

41
[ 29241-60-9 ]
[ 96797-15-8 ]
C₂₈H₂₂ClN₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		A. 4- (6-CHLORO-5-METHYL-3-PYRIDYL) imidazole. To a solution of 4-iodo- 1-TRITYL-LH-IMIDAZOLE (25 g, 57. 3 mmoles) in THF (250 ml) at room temperature was added ethylmagnesium bromide (69 ml, 69 mmoles) under dry conditions. After stirring for 90 minutes, zinc chloride (9.4 g, 68.6 mmoles) was added to the reaction mixture. After stirring for another 90 minutes, tetrakis (triphenylphosphine) palladium (6.6 g, 5.72 mmoles) and <strong>[29241-60-9]5-bromo-3-methyl-2-chloropyridine</strong> (14.2 g, 68.6 mmoles) were added to the reaction mixture. Following that, the reaction mixture was heated in a 70C oil bath overnight. Upon cooling, the reaction was diluted with dichloromethane and washed with an EDTA buffer (at approximate pH 9) (300 ml), NACI (sat. ) (150 ml), dried over sodium sulfate, filtered, and concentrated. To the crude material in DCM (250 ML) at room temperature was added trifluoroacetic acid (115 ml, 1.5 moles). After stirring for 90 minutes, the excess TFA and DCM were removed IN VACUO. The crude product was left under high vacuum pump overnight. To the crude product was added 60 ml of 3 N HC1 and the mixture was left in the sonicator for 120 minutes. Once recovered from the sonicator, the mixture was filtered and the aqueous solution was washed with diethyl ether until the organic phase was no more UV active. The aqueous solution was cooled to 0C and 30% NaOH solution was added until an approximate pH 7-8 was obtained. The obtained solid product was filtered and dried over night under high vacuum pump to yield 2- CHLORO-5-(LH-IMIDAZOL-4-YL)-3-METHYL-PYRIDINE (8.156 g, 74%). MH+ (194)
		To a solution of 4-IODO-1-TRITYL-LH- imidazole (25 g, 57.3 mmoles) in THF (250 ml) at room temperature was added ethylmagnesium bromide (69 ml, 69 mmoles) under dry conditions. After stirring for 90 minutes, zinc chloride (9.4 g, 68.6 mmoles) was added to the reaction mixture. After stirring for another 90 minutes, tetrakis (triphenylphosphine) palladium (6.6 g, 5.72 mmoles) and <strong>[29241-60-9]5-bromo-3-methyl-2-chloropyridine</strong> (14.2 g, 68.6 mmoles) were added to the reaction mixture. Following that, the reaction mixture was heated in a 70C oil bath overnight. Upon cooling, the reaction was diluted with dichloromethane and washed with an EDTA buffer (at approximate pH 9) (300 ml), NACL (sat. ) (150 ml), dried over sodium sulfate, filtered, and concentrated. To the crude material in DCM (250 ml) at room temperature was added trifluoroacetic acid (115 ML, 1.5 moles). After stirring for 90 minutes, the excess TFA and DCM were removed in vacuo. The crude product was left under high vacuum pump overnight. To the crude product was added 60 ml of 3N HCI and the mixture was left in the sonicator for 120 minutes. Once recovered from the sonicator, the mixture was filtered and the aqueous solution was washed with diethyl ether until the organic phase was no more LTV active. The aqueous solution was cooled to 0C and 30% NaOH solution was added until an approximate pH 7-8 was obtained. The obtained solid product was filtered and dried over night under high vacuum pump to yield 2-CHLORO-5- (LH-IMIDAZOL-4- yl)-3-methyl-pyndine (8.156 g, 74%). MH+ (194)

Reference： [1]Patent: WO2004/96822,2004,A2 .Location in patent: Page 276; 277
[2]Patent: WO2004/96823,2004,A2 .Location in patent: Page 58; 59

42
[ 56423-63-3 ]
[ 96797-15-8 ]
5-(1H-imidazol-4-yl)-pyrazine dihydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
37%		To a solution of 4-IODO-1-TRITYL-LH-IMIDAZOLE (1 eq) in THF at room temperature was added ethylmagnesium bromide (1.2 eq) under dry conditions. After stirring for 90 minutes, zinc chloride (1.2 eq) was added to the reaction mixture. After stirring for another 90 minutes, tetrakis (triphenylphosphine) palladium (10%) and 5- <strong>[56423-63-3]bromopyrazine</strong> (1.3 eq) were added to the reaction mixture. Subsequent reaction conditions and work up are as described previously in Example 73, the resulting solid 2-(LH-IMIDAZOL-4-YL)-PYRAZINE (37%) was collected by filtration. MH (147)

Reference： [1]Patent: WO2004/96822,2004,A2 .Location in patent: Page 244

43
[ 52200-48-3 ]
[ 96797-15-8 ]
C₂₇H₂₀ClN₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		A. 4- (2-chloro-3-pyridyl) imidazole. To a solution of 4-iodo-1-trityl- 1H imidazole (25 g, 57. 3 mmoles) in THF (285 ml) at room temperature was added ethylmagnesium bromide (69 ml, 68.8 mmoles) under dry conditions. After STIRRING for 90 minutes, zinc chloride (9.37 g, 68.8 mmoles) was added to the reaction mixture. After stirring for another 90 minutes, tetrakis (triphenylphosphine) palladium (5 g, 4.3 mmoles) and <strong>[52200-48-3]3-bromo-2-chloropyridine</strong> (13.2 g, 68.8 mmoles) were added to the reaction mixture. Following that, the reaction mixture was heated in a 70C oil bath overnight. Upon cooling, the reaction was diluted with dichloromethane (1 L) and washed with a 30% NaOH solution containing an added 40 g of EDTA (3x 400 ml), with NACI (sat. ) (300 ml), dried over MGS04, filtered, and concentrated. To the crude material was added dichloromethane (200 ml) and trifluoroactetic acid (60 ml). After standing for 1 hour, the reaction was concentrated and pumped on overnight. To the resulting oily tar was added 1M HCl (60 ml) and the mixture was sonicated for 30 minutes and than filtered. The aqueous filtrate was washed with diethyl ether (2x 100 ml). The aqueous layer was cooled in an ice bath and the pH was adjusted by addition of a 30% NaOH solution until the pH was approximately 9-10. The resulting solid was filtered, rinsed with cold water (20 ml), rinsed with diethyl ether (20 ml), and pumped on yielding 4- (2-chloro-3-pyridyl) imidazole (8.43 g, 82%). MH+ (180)
		To a solution of 4-IODO-1-TRITYL-LH-IMIDAZOLE (25 g, 57.3 mmoles) in THF (285 ml) at room temperature was added ethylmagnesium bromide (69 ml, 68.8 mmoles) under dry conditions. After stirring for 90 minutes, zinc chloride (9.37 g, 68.8 mmoles) was added to the reaction mixture. After stirring for another 90 minutes, tetrakis (triphenylphosphine) palladium (5 g, 4.3 mmoles) and <strong>[52200-48-3]3-bromo-2-chloropyridine</strong> (13.2 g, 68.8 mmoles) were added to the reaction mixture. Following that, the reaction mixture was heated in a 70C oil bath overnight. Upon cooling, the reaction was diluted with dichloromethane (1 L) and washed with a 30% NaOH solution containing an added 40 g of EDTA (3x 400 ml), with NACI (sat. ) (300 ML), dried over MGSO4, filtered, and concentrated. To the crude material was added dichloromethane (200 ml) and TRIFLUOROACTETIC acid (60 ml). After standing for 1 hour, the reaction was concentrated and pumped on overnight. To the resulting oily tar was added 1M HC1 (60 ml) and the mixture was sonicated for 30 minutes and than filtered. The aqueous filtrate was washed with diethyl ether (2x 100 ml). The aqueous layer was cooled in an ice bath and the pH was adjusted by addition of a 30% NaOH solution until the pH was approximately 9-10. The resulting solid was filtered, rinsed with cold water (20 ml), rinsed with diethyl ether (20 ml), and pumped on yielding 4- (2-chloro-3-pyridyl) imidazole (8.43 g, 82%). MH+ (180)

Reference： [1]Patent: WO2004/96822,2004,A2 .Location in patent: Page 274
[2]Patent: WO2004/96823,2004,A2 .Location in patent: Page 56; 57

44
[ 38696-20-7 ]
[ 96797-15-8 ]
[ 1217902-45-8 ]

Yield	Reaction Conditions	Operation in experiment
65%		To a solution of 4-Iodo-1-trityl-1H-imidazole (Synthonix, 2.0 g, 4.58 mmol) in THF (50 mL) at room temperature was added ethylmagnesium bromide (Aldrich, 1.0 M solution in THF, 5.5 mL, 5.50 mmol) under dry conditions. After stirring for 90 minutes, zinc chloride (Aldrich, 0.749. g, 5.50 mmol) was added to the reaction mixture. After stirring for an additional 90 minutes, tetrakis(triphenyl)phosphine)palladium (Strem, 0.529 g, 0.46 mmol) and <strong>[38696-20-7]5-bromo-2-phenylpyrimidine</strong> (as prepared in Example 1, step A, 1.29 g, 5.50 mmol) were added to the reaction mixture. The reaction mixture was heated in a 70° C. oil bath overnight. Upon cooling, the reaction was diluted with dichloromethane and washed with 0.5 M EDTA buffer (at pH ~9) (2*250 mL) followed by brine (150 mL). The organics were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by flash silica column chromatography using an 80 g Silicycle.(R). column (elution with 10-30percent ethyl acetate in hexane) which afforded the desired intermediate, 2-phenyl-5-(1-trityl-1H-imidazol-4-yl)pyrimidine, as a white solid (1.38 g, 65percent). Rf 0.87 with 95:5 v/v dichloromethane-methanol; 1H-NMR (400 MHz; DMSO-d6) delta 9.29 (s, 2H), 8.42 (m, 2H), 7.92 (d, 1H), 7.62 (d, 1H), 7.56-7.43 (m, 13H), 7.24-7.22 (m, 6H); MS (ESI-) m/z 463.0 (M-1); H-PGDS FPBA IC50: >20 muM.

Reference： [1]Patent: US2010/75990,2010,A1 .Location in patent: Page/Page column 39

45
[ 875479-34-8 ]
[ 96797-15-8 ]
[ 1242440-99-8 ]

Yield	Reaction Conditions	Operation in experiment
71.8%		3 M EtMgBr in diethyl ether (4.58 mL, 13.75 mmol) was added slowly to a solution of4-iodo-l-trityl-lH-imidazole (5 g, 11.46 mmol) 100 mL of THF and stirred at rt. After 30 min, ZnCl2 (3.12 g, 23 mmol) was added and the mixture was stirred at rt for 1 h. The Intermediate 2 (3.08 g, 11.46 mmol) was added, followed by Pd(PPh3)4 (662 mg, 0.573 mmol), and the reaction mixture was heated at reflux for 4 hours. At this point, the LCMS indicated 100% conversion to product (rt- 1.19 min). The reaction was cooled to rt, quenched with aqueous NH4CI (30 ml). The inorganic salts crashed out, which was removed by filtration. The aqueous layer was separated, and the organic was washed with water (30 mL) and brine (30 mL). The organic layer was dried (MgSO4), filtered, and evaporated in vacuo. The residue was purified by flash chromatography (10-80% EA in hexanes) to give 4.1 g (yield 71.8%) of ethyl (lS,2S)-2-[4-(l- trityl-lH-imidazol-4-yl)phenyl3cyclopropanecarboxylate. LCMS: m/z 499 (M+H)+.

Reference： [1]ACS Medicinal Chemistry Letters,2013,vol. 4,p. 509 - 513
[2]Patent: WO2010/101724,2010,A1 .Location in patent: Page/Page column 31-32

46
[ 1122-72-1 ]
[ 96797-15-8 ]
[ 880652-82-4 ]

Yield	Reaction Conditions	Operation in experiment
~ 99%		A mixture of 4-iodo-1-tritylimidazole (commercially available) (5.0 g, 11.5 mmol) in dichloromethane (50 mL) at -10 C. was treated with ethyl magnesium bromide (3.8 mL, 11.5 mmol, 3M in ether) and allowed to react for 90 m. A solution of 6-methyl-pyridine-2-carbaldehyde (Intermediate D1) (commercially available from Aldrich) (0.93 g, 7.7 mmol) in dichloromethane (10 mL) was added via syringe at -10 C. and stirred for 45 m. The mixture was quenched with water (50 mL) and with a saturated solution of ammonium chloride (60 mL). The residue was isolated in an aqueous workup, extracting with CHCl3 and purified by chromatography on silica gel with 5% NH3-MeOH:CH2Cl2 to give (6-Methyl-pyridin-2-yl)-(1-trityl-1H-imidazol-4-yl)-methanol (Intermediate D2) as a solid, 3.3 g (99%). A solution of (6-methyl-pyridin-2-yl)-(1-trityl-1H-imidazol-4-yl)-methanol (Intermediate D2) (3.7 g, 8.5 mmol) in dioxane (75 mL) was treated with activated manganese(IV) oxide (MnO2), (commercially available from Aldrich): (7 g, 80 mmol) at 90 C. for 20 m. The mixture was filtered through Celite and the solvent was removed under vacuum. The product, (6-methyl-pyridin-2-yl)-(1-trityl-1H-imidazol-4-yl)-methanone (Intermediate D3) was used in the next step without further purification 3.6 g. Methyl triphenylphosphine bromide (commercially available from Aldrich) (2.2 g, 6.16, mmol) in THF(60 mL) at -70 C. was treated with nBuLi (2.44 mL, 2.5M in hexane). The reaction mixture warmed to -50 C. in 1 h. A solution of (6-methyl-pyridin-2-yl)-(1-trityl-1H-imidazol-4-yl)-methanone (Intermediate D3) (1.38 g, 3.2 mmol) in THF (25 mL) was added to the mixture via syringe at -50 C. The mixture was allowed to warm to rt for 1.5 h. The mixture was poured into ether (mL) and washed with water (2×10 mL). The organic solution was dried over MgSO4, filtered and evaporated to leave a residue. This was purified by chromatography on SiO2 with diethyl ether to give 2-methyl-6-[1-(1-trityl-1H-imidazol-4-yl)-vinyl]-pyridine (Intermediate D4) 0.68 g (50%). A mixture of 2-methyl-6-[1-(1-trityl-1H-imidazol-4-yl)-vinyl]-pyridine (Intermediate D4) (460 mg, 1.1 mmol) in trifluoroacetic acid (TFA) (25 mL) was reduced by the action of 10% Pd/C (100 mg) under H2 at 35 psi for 20 h at rt. The mixture was filtered through Celite and freed of solvent under reduced pressure. The residue was purified by chromatography on silica gel with 5% NH3-MeOH:CH2Cl2 to give 2-[1-(1H-imidazol-4-yl)-ethyl]-6-methyl-pyridine (Intermediate D5) as a solid, 150 mg (93%). A mixture of 2-[1-(1H-imidazol-4-yl)-ethyl]-6-methyl-pyridine (Intermediate D5) (150 mg, 0.80 mmol) in THF (8 mL) and water (8 mL) was treated with NaHCO3 (240 mg, 2.86 mmol) and phenylchlorothionoformate (0.35 mL, 2.60 mmol) for 3 h at rt. The mixture was diluted with diethyl ether (35 mL) and water (10 mL). The aqueous layer was removed and extracted with ether (2×10 mL). The organic layers were combined, dried over MgSO4, filtered and concentrated under vacuum. The residue was treated with triethylamine (1 mL) in methanol (9 mL) at rt for 16 h. The solvent was removed and the product was isolated and purified either by tituration with CH2Cl2: hexane or by chromatography on SiO2 with EtOAc or 3 to 7% NH3-MeOH:CH2Cl2. This gave 4-[1-(6-methyl-pyridin-2-yl)-ethyl]-1,3-dihydro-imidazole-2-thione (Compound 9) 50 mg (30%). 1H NMR (300 MHz, DMSO-d6 w/TMS) delta11.9 (s, 1H), 11.7 (s, 1H), 7.60 (t, J=7.5 Hz, 1H), 7.07 (d, J=7.5 Hz, 1H), 7.02 (d, J=7.5 Hz, 1H), 6.53 (s, 1H), 3.95 (q, J=6.9 Hz, 1H), 2.42 (s, 3H), 1.46 (d, J=7.2 Hz, 3H).

Reference： [1]Patent: US2006/69143,2006,A1 .Location in patent: Page/Page column 19-20

47
[ 96797-15-8 ]
[ 106976-44-7 ]
[ 945408-09-3 ]

Yield	Reaction Conditions	Operation in experiment
90%		d) Rac-(2-Ethyl-6-methyl-phenyl)-( 1-trityl- lH-imidazol-4-yl)-methanolThis compound was prepared using methodology described in J. Org. Chem. 1991, 56, 5739-5740. To a stirred suspension of 1.47 g (3.37 mmol) 4-iodo-tritylimidazole in 5 ml dichloromethane was added dropwise 1.12 ml (3.37 mmol) of a 3 M solution of ethylmagnesium bromide in diethyl ether at such a rate that the temperature of the reaction mixture did not rise above 28 0C. The resulting solution of ( 1-trityl- IH- imidazo 1-4- yl) -magnesium halide was stirred at room temperature for 30 minutes, and then a solution of 0.50 g (3.37 mmol) 2-ethyl-6-methyl-benzaldehyde in 2 ml dichloromethane was added dropwise over 10 minutes. The reaction mixture was then stirred at room temperature for 5 h, before being quenched by dropwise addition of water and diluted with dichloromethane. The phases were separated and the organic phase was dried over Na2SO4, filtered and concentrated in vacuo to afford 1.40 g (90%) of the title compound as an off-white foam which was used in the next step without further purification.

Reference： [1]Patent: WO2007/85556,2007,A2 .Location in patent: Page/Page column 51

48
[ 1167625-98-0 ]
[ 96797-15-8 ]
[ 1167626-21-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; palladium diacetate; CyJohnPhos; In 1-methyl-pyrrolidin-2-one; water; toluene; at 100℃; for 0.25h;Inert atmosphere; Microwave irradiation;	Intermediate 6: Ethyl 6-(1-triphenylmethyl-1H-imidazol-4-yl)imidazo[1,2-alpha]pyridine-2-carboxylate and 6-(1-triphenylmethyl-1H-imidazol-4-yl)imidazo[1,2-alpha]pyridine-2-carboxylic acid 6.1: Ethyl 6-(1-triphenylmethyl-1H-imidazol-4-yl)imidazo[1,2-alpha]pyridine-2-carboxylate 873 mg of 4-iodo-1-(triphenylmethyl)imidazole, 750 mg of 2-ethoxycarbonyl-imidazo[1,2-alpha]pyridine-6-boronic acid, 23 mg of palladium acetate and 70 mg of (2-biphenyl)-dicyclohexylphosphine are degassed under vacuum and then suspended, under argon, in a degassed mixture of 15 ml of toluene, 5 ml of water and 5 ml of N-methylpyrrolidone. After addition of 950 mg of potassium phosphate, the mixture is degassed under vacuum, then placed under argon and heated at 100 C. for 15 minutes under microwave irradiation, and then cooled, diluted and stirred in a mixture of 50 ml of saturated sodium bicarbonate solution and 50 ml of dichloromethane. The organic phase is dried over sodium sulphate, filtered and concentrated to dryness under reduced pressure. The residue is chromatographed on silica, elution being carried out with a mixture of ethyl acetate and hexane. The fractions comprising the expected product are combined and concentrated to dryness under reduced pressure to give 508 mg of ethyl 6-(1-triphenylmethyl-1H-imidazol-4-yl)imidazo[1,2-alpha]pyridine-2-carboxylate.1H NMR spectrum (d6-DMSO, delta in ppm): 8.97 (s, 1H), 8.54 (s, 1H), 7.76-7.72 (m, 1H), 7.56-7.52 (m, 3H), 7.47-7.37 (m, 9H), 7.20-7.17 (m, 6H), 4.31-4.27 (m, 2H), 1.34-1.20 (m, 3H).Mass spectrum (APCI): m/z=499 [M+H]+.
	With potassium phosphate; CyJohnPhos;palladium diacetate; In 1-methyl-pyrrolidin-2-one; water; toluene; at 100℃; for 0.25h;Inert atmosphere; Microwave irradiation;	13.1: Ethyl 6-(1-triphenylmethyl-1H-imidazol-4-yl)imidazo[1,2-a]pyridine-2-carboxylate 873 mg of 4-iodo-1-triphenylmethylimidazole, 750 mg of 2-ethoxycarbonylimidazo[1,2-a]pyridine-6-boronic acid, 23 mg of palladium acetate and 70 mg of (2-biphenyl)dicyclohexyl-phosphine are degassed under vacuum and then suspended, under argon, in a degassed mixture of 15 mL of toluene, 5 mL of water and 5 mL of N-methylpyrrolidone. After addition of 950 mg of potassium phosphate, the mixture is degassed under vacuum and then placed under argon and heated for 15 minutes at 100 C. by microwave, then cooled, diluted and stirred in a mixture of 50 mL of saturated sodium bicarbonate solution and 50 mL of dichloromethane. The organic phase is dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure. The residue is chromatographed on silica, eluding with a mixture of ethyl acetate and hexane. The fractions containing the expected product are combined and concentrated to dryness under reduced pressure to give 508 mg of ethyl 6-(1-triphenylmethyl-1H-imidazol-4-yl)imidazo[1,2-a]pyridine-2-carboxylate. 1H NMR spectrum (DMSO-d6, delta in ppm): 8.97 (s, 1H), 8.54 (s, 1H), 7.76-7.72 (m, 1H), 7.56-7.52 (m, 3H), 7.47-7.37 (m, 9H), 7.20-7.17 (m, 6H), 4.31-4.27 (m, 2H), 1.34-1.20 (m, 3H). Mass spectrum (APCI): m/z=499 [M+H]+.
	With potassium phosphate;palladium diacetate; CyJohnPhos; In 1-methyl-pyrrolidin-2-one; water; toluene; at 100℃; for 0.25h;Inert atmosphere;	873 mg of 4-iodo-1-triphenylmethylimidazole, 750 mg of 2-ethoxycarbonylimidazo[1,2-a]pyridine-6-boronic acid, 23 mg of palladium acetate and 70 mg of (2-biphenyl)dicyclohexyl-phosphine are degassed under vacuum and then suspended, under argon, in a degassed mixture of 15 mL of toluene, 5 mL of water and 5 mL of N-methylpyrrolidone. After addition of 950 mg of potassium phosphate, the mixture is degassed under vacuum and then placed under argon and heated for 15 minutes at 100 C. by microwave, then cooled, diluted and stirred in a mixture of 50 mL of saturated sodium bicarbonate solution and 50 mL of dichloromethane. The organic phase is dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure. The residue is chromatographed on silica, eluding with a mixture of ethyl acetate and hexane. The fractions containing the expected product are combined and concentrated to dryness under reduced pressure to give 508 mg of ethyl 6-(1-triphenylmethyl-1H-imidazol-4-yl)imidazo[1,2-a]pyridine-2-carboxylate. 1H NMR spectrum (DMSO-d6, delta in ppm): 8.97 (s, 1H), 8.54 (s, 1H), 7.76-7.72 (m, 1H), 7.56-7.52 (m, 3H), 7.47-7.37 (m, 9H), 7.20-7.17 (m, 6H), 4.31-4.27 (m, 2H), 1.34-1.20 (m, 3H). Mass spectrum (APCI): m/z=499 [M+H]+.

Reference： [1]Patent: US2010/317656,2010,A1 .Location in patent: Page/Page column 10
[2]Patent: US2010/317675,2010,A1 .Location in patent: Page/Page column 17
[3]Patent: US2010/317686,2010,A1 .Location in patent: Page/Page column 10

49
[ 1300730-84-0 ]
[ 925-90-6 ]
[ 96797-15-8 ]
[ 1300730-85-1 ]

Yield	Reaction Conditions	Operation in experiment
29%		Example 68 (2R,5S)-2-isopropyl-3,6-dimethoxy-5-(2-(l-trityl-l H-imidazol-4- y phenethy l)-2,5 -dihydropy razine; [0398) To a stirred solution of 4-iodo-1-trityl-lH-imidazole (300 mg, 0.688 mmol) in anhydrous THF (4 mL) at room temperature was added EtMgBr (1.0 M in THF, 0.802 mmol, 0.8 mL) dropwise, under an atmosphere of N2. The resulting solution was allowed to stir for 90 min and anhydrous ZnCl2 (109 mg, 0.802 mmol) was added. The resulting white suspension was allowed to stir for 90 min and a solution of the (2S,5R)-2-(2-iodophenethyl)- 5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine (237 mg, 0.573 mmol) in THF (1 mL) was added followed by the immediate addition of Pd(PPh3)4 (33 mg, 0.029 mmol). The reaction mixture was allowed to stir at 70 C for 12 h under an atmosphere of N2. After cooling to room temperature, the solution was diluted with CH2CI2 (10 mL) and the organic layer was washed with an EDTA (aq) buffer (pH = 9) (2 x 5 mL) and brine. The organic layer was dried (Na2S04) and concentrated under reduced pressure. The crude residue was purified by flash column chromatography to afford the desired product as yellow oil (87 mg, 0.146 mmol, 29%). NMR: 0.70 (d, 3H, J = 6 Hz), 1.02 (d, 3H, J = 7.2 Hz), 1.72-1.81 (m, 1H), 2.01- 2.08 (m, 1 H), 2.15-2.24 (m, 1 H), 2.80-3.09 (m, 2H), 3.54 (s, 3H), 3.56 (s, 3H), 3.86-3.91 (m, 2H), 6.94 (d, 1 H, J = 1.2 Hz), 7.15-7.22 (m, 9H), 7.27 (d, 1H, J = 1.6Hz), 7.32-7.36 (m, 8H), 7.48 (d, 1 H, J= 1.2 Hz), 7.58-7.61 (m, 1 H).

Reference： [1]Patent: WO2011/56652,2011,A1 .Location in patent: Page/Page column 141

50
[ 96797-15-8 ]
[ 31462-54-1 ]
C₂₆H₂₀N₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 28 General Procedure for the Palladium-Catalyzed Cross-Coupling of ArylIodides with l -Trityl-lH-imidazol-4-yl)zinc(II) chloride; ,[0349] To a stirred solution of 4-iodo-1-trityl-lH-imidazole (218.0 mg, 0.5 mmol) in anhydrous THF (4 mL) at room temperature was added EtMgBr (1.0 M in THF, 0.5 mmol, 0.5 mL) dropwise, under an atmosphere of N2. The resulting solution was allowed to stir for 90 min and anhydrous ZnCl2 (0.5 mmol, 68.2 mg) was added. The resulting white suspension was allowed to stir for 90 min and a solution of the aryl iodide (0.5 mmol) in THF (1 mL) was added followed by the immediate addition of Pd(PPlV}) (56 mg, 0.05 mmol). The reaction mixture was allowed to stir at 70 C for 12 h under an atmosphere of N2. After cooling to room temperature, the solution was diluted with CH2C12 (10 mL) and the organic layer was washed with an EDTA (aq) buffer (pH = 9) (2 x 5 mL) and brine. The organic layer was dried (Na2SC>4) and concentrated under reduced pressure. The crude residue was used in next step without further purification. To a solution of the crude imidazole from the previous step was added trifluoroacetic acid (1.0 mL) and MeOH (4.0 mL). The solution was stirred at 80 C for 2 h. The reaction mixture was allowed to cool to room temperature and the pH was adjusted to -10 with 10% NaOH (aq). The aqueous phase was extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with water, brine, and dried. The solvent was removed in vacuo to afford the crude residue, which was purified by flash column chromatography on silica gel to afford the desired product.

Reference： [1]Patent: WO2011/56652,2011,A1 .Location in patent: Page/Page column 114

51
(1SR,2RS)-2-(4-chlorophenyl)spiro[cyclopropane-1,3'-indolin]-2'-one [ No CAS ]
[ 96797-15-8 ]
(1RS,2SR)-2-(4-chlorophenyl)-1'-(1-trityl-1H-imidazol-4-yl)spiro[cyclopropane-1,3'-indolin]-2'-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With potassium carbonate;copper(l) iodide; N,N-dimethylethylenediamine; In acetonitrile; at 80℃; for 21h;Inert atmosphere;	(1S,2R) and (1R,2S)-2-(4-chlorophenyl)-1'-(1-trityl-1H-imidazol-4-yl)spiro[cyclopropane-1,3'-indolin]-2'-one <strong>[96797-15-8]4-Iodo-1-trityl-1H-imidazole</strong> (210 mg, 0.48 mmol) was added to a suspension of racemic (1S,2R)-2-(4-chlorophenyl)spiro[cyclopropane-1,3'-indolin]-2'-one (107 mg, 0.4 mmol) in acetonitrile (2 mL) under a nitrogen atmosphere. A steady stream of nitrogen was bubbled through the suspension as it was heated to 40 C. over 15 minutes. Potassium carbonate (110 mg, 0.8 mmol), copper (I) iodide (12 mg, 15 mol %), and N,N-dimethylethylenediamine (0.12 mmol, 30 mol %) were added and the reaction mixture was heated to 80 C. and kept for 21 hours under nitrogen atmosphere. The mixture was cooled to room temperature, filtered and concentrated to give the title product. The residue was purified by flash column chromatography (gradient elution, 5-10% ethyl acetate in petroleum ether) to give racemic trans-2-(4-chlorophenyl)-1'-(1H-imidazol-4-trityl)spiro[cyclopropane-1,3'-indolin]-2'-one (157 mg, 68%). LC/MS m/e calcd. for C38H28ClN3O: 577, observed (M+H)+: 578.2 MS calcd. for C38H28ClN3O 578, obsd. (ESI+) [(M+H)+] 579.3.
68%	With potassium carbonate;copper(l) iodide; N,N-dimethylethylenediamine; In acetonitrile; at 80℃; for 21h;Inert atmosphere;	Example 80(IS, 2R) and (1R, 2S)-2-(4-(2-(4-chlorophenyl)-2'-oxospiro[cyclopropane-l,3'- indoline] - 1 '-yl) - 1 H-imidazol- 1 -yl)acetic acid(IS, 2R) and (1R, 2S)-2-(4-chlorophenyl)-l'-(l-trityl-lH-imidazol-4- yl) spiro [cyclopropane- 1 ,3'-indolin] -2'-one4-Iodo-l-trityl-lH-imidazole (210 mg, 0.48 mmol) was added to a suspension of racemic (IS, 2R)-2-(4-chlorophenyl)spiro[cyclopropane-l,3'-indolin]-2'-one (107 mg, 0.4 mmol) in acetonitrile (2 mL) under a nitrogen atmosphere. A steady stream of nitrogen was bubbled through the suspension as it was heated to 40 C over 15 minutes. Potassium carbonate (110 mg, 0.8 mmol), copper (I) iodide (12 mg, 15 mol %), and N,N- dimethylethylenediamine (0.12 mmol, 30 mol %) were added and the reaction mixture was heated to 80 C and kept for 21 hours under nitrogen atmosphere. The mixture was cooled to room temperature, filtered and concentrated to give the title product. The residue was purified by flash column chromatography (gradient elution, 5-10% ethyl acetate in petroleum ether) to give racemic trans-2-(4-chlorophenyl)-l'-(lH-imidazol-4- trityl)spiro[cyclopropane-l,3'-indolin]-2'-one(157 mg, 68%). LC/MS m/e calcd. for C38H28C1N30: 577, observed (M+H)+: 578.2MS calcd. for C38H28ClN30 578, obsd. (ESP) [(M+H)+] 579.3.
68%	With potassium carbonate;copper(l) iodide; N,N-dimethylethylenediamine; In acetonitrile; at 80℃; for 21h;Inert atmosphere;	Example 80; (IS, 2R) and (1R, 2S)-2-(4-(2-(4-chlorophenyl)-2'-oxospiro[cyclopropane-l,3'- indoline] - 1 '-yl)- lH-imidazol- l-yl)acetic acid; Synthesis of (IS, 2R) and (1R, 2S)-2-(4-chlorophenyl)-l'-(l-trityl-lH-imidazol-4- yl)spiro[cyclopropane-l,3'-indolin]-2'-one4-Iodo-l-trityl-lH-imidazole (210 mg, 0.48 mmol) was added to a suspension of racemic (I S, 2R)-2-(4-chlorophenyl)spiro[cyclopropane-l,3'-indolin]-2'-one (107 mg, 0.4 mmol) in acetonitrile (2 mL) under a nitrogen atmosphere. A steady stream of nitrogen was bubbled through the suspension as it was heated to 40 C over 15 minutes. Potassium carbonate (1 10 mg, 0.8 mmol), copper (I) iodide (12 mg, 15 mol %), and N,N- dimethylethylenediamine (0.12 mmol, 30 mol %) were added and the reaction mixture was heated to 80 C and kept for 21 hours under nitrogen atmosphere. The mixture was cooled to room temperature, filtered and concentrated to give the title product. The residue was purified by flash column chromatography (gradient elution, 5-10% ethyl acetate in petroleum ether) to give racemic trans-2-(4-chlorophenyl)-l'-(lH-imidazol-4- trityl)spiro[cyclopropane-l,3'-indolin]-2'-one(157 mg, 68%). LC/MS m/e calcd. for C38H28C1N30: 577, observed (M+H)+: 578.2MS calcd. for C38H28C1N30 578, obsd. (ESf) [(M+H)+] 579.3.

Reference： [1]Patent: US2011/144106,2011,A1 .Location in patent: Page/Page column 54
[2]Patent: WO2011/70039,2011,A1 .Location in patent: Page/Page column 99-100
[3]Patent: WO2011/69298,2011,A1 .Location in patent: Page/Page column 105-106

52
[ 1252858-34-6 ]
[ 96797-15-8 ]
C₅₁H₇₂N₆O₄Si₃ [ No CAS ]
[ 15469-97-3 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 5498 - 5507

53
[ 40138-16-7 ]
[ 96797-15-8 ]
[ 1402838-08-7 ]

Yield	Reaction Conditions	Operation in experiment
75.6%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 90℃;Inert atmosphere;	2-formylbenzeneboronic acid (1.55 g, 6.88 mmol),1-trityl-4-iodoimidazole (3.0 g, 4.59 mmol),Potassium phosphate (4.38 g, 13.77 mmol),Pd(PPh3)4 (0.3g, 10%, w/w%) was added to DMF (30mL)In a mixed solution with water (6 mL), the system was replaced with nitrogen 4 times.The reaction was carried out at 90 C overnight under a nitrogen atmosphere. TLC detects complete reaction,Cooled to room temperature, filtered and the filtrate was diluted with ethyl acetate (300 mL).Wash three times with water (100 mL), and dilute the organic phase under reduced pressure.The residue is separated by flash column chromatography.The target product was 2.15g,The yield was 75.6%.
72%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 100℃; for 16h;Inert atmosphere;	A mixture of 4-iodo-1-(triphenylmethyl)-1H-imidazole (Intermediate A, 4.36 g, 9.99 mmol), (2-formylphenyl)boronic acid (1.65 g, 11.00 mmol), Pd(PPh3)4 (1.16 g, 1.0 mmol) and K3PO4 (4.25 g, 20.02 mmol) in DMF (40 mL) and water (8 mL) was stirred at 100 C. for 16 h under N2 atmosphere. The reaction mixture was diluted with water (100 mL) and extracted with ethyl acetate (150 mL*2). The organic phases were combined, washed with brine and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was purified by flash chromatography eluting with EtOAc in hexane (1% to 25% gradient) to yield 2-(1-trityl-1H-imidazol-4-yl)benzaldehyde as yellow solid (3 g, 72%). MS: m/z=415.1 [M+H]+.
66.7%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 90℃; for 16h;Inert atmosphere;	A suspensionof 4 (3.0 g, 6.9 mmol), the appropriate 2-formyl boronic acid(1.6 g, 10.7 mmol) and K3PO4 (4.4 g, 20.8 mmol) in DMF (30 mL) andwater (6 mL) was purged with nitrogen for 5 min, followed by theaddition of Pd(PPh3)4 (0.6 g, 0.5 mmol) and the mixturewas purgedwith nitrogen for another 5 min. The reaction mixture was stirredat 90 C for 16 h under an atmosphere of N2. The solution wasallowed to cool and was filtered through a plug of celite. Themixture was diluted with water (50 mL) and was extracted withethyl acetate to afford the crude product which was purified byflash column chromatography on silica gel to yield 6 as a white solid(1.9 g, 66.7%). Mp 147e149 C. 1H NMR (300 MHz, Chloroform-d)d(ppm) 7.97 (dd, J 7.8, 1.4 Hz, 1H), 7.72e7.54 (m, 3H), 7.38 (h,J 3.2 Hz,11H), 7.25e7.19 (m, 6H), 7.07 (d, J 1.3 Hz, 1H). MS (EI) m/z 415.2 [MH].

66.7%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 90℃; for 16h;Inert atmosphere;	3 (3.0 g, 6.9 mmol),Formylbenzeneboronic acid (1.6 g, 10.7 mmol),K3PO4 (4.4 g, 20.8 mmol) was dissolved in DMF (30 mL) and water (6 mL)Pd (PPh3) 4 (0.6 g, 0.5 mmol) was added,N2 protection at 90 C for 16 hours,Cooling, suction filtration,Water (50 mL) was added, extracted with ethyl acetate,Dried over anhydrous magnesium sulfate,Column chromatography gave a white solid,Yield 66.7%
63%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 100℃;Inert atmosphere;	General procedure: 4-Iodo-1-trityl-1H-imidazole (5, 2 g, 4.58 mmol), (5-chloro-2-methoxyphenyl)boronic acid(0.852 g, 4.58 mmol), K3PO4 (2.9 g, 13.7 mmol), Pd(PPh3)4 (0.74 g, 0.64 mmol) were added todry dimethylformamide (30 mL). The reaction mixture was stirred at 100 C under inert atmosphere,until the starting material disappeared in TLC. The reaction mixture was distilled in vacuo, and ethylacetate (100 mL) was added to the mixture. The organic extract was washed twice with saturatedaqueous NaCl (20 mL), and the organic extract was dried over Na2SO4. After solvent was removedunder vacuum, the product was purified as a white solid by silica gel column chromatography, 1.2 g,yield 63%.
60%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 90℃;Inert atmosphere;	[270] To a solution of (2-forrnylphenyl)boronic acid (2.0 g, 13.3 rnrnol) in a rnixed solvent of N,N- dirnethylforrnarnide (DMF) (60 rnL) and water (12 rnL) was successively added 4-iodo-1- trityl-1H-irnidazole (6.1 g, 14.0 rnrnol), and potassiurn phosphate (5.6 g, 26.6 rnrnol). After degassing with nitrogen, the resulted rnixture was added tetrakis(triphenylphosphine)palladiurn(0) (Pd(PPh3)4) (300 rng, 0.26 rnrnol). The resulted rnixture was degassed with nitrogen and stirred at 90C for overnight under nitrogen. And then the rnixture was cooled down to roorn ternperature and filtered, the filtrate was added water (60 rnL), extracted with ethyl acetate (100 rnLx2). The cornbined organic phase was washed with brine (25 rnL), dried over sodiurn sulfate, filtered and concentrated. The residue was purifiedby colurnn chrornatography on silica gel (petroleurn ether: ethyl acetate= 6:1) to afford cornpound 1.1 (3.3 g, yield: 60%) as a white solid.[271] rn/z: [M+H]415
54%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 90℃; for 6h;Inert atmosphere;	Under nitrogen protection,Tetrakistriphenylphosphine palladium (2.0 g, 1.7 mmol, 0.074 eq), 4-iodo-1-trityl-1H-imidazole (0102-1) (10.0 g, 23.0 mmol, 1.0 eq),2-aldehyde phenylboronic acid (0103-1) (4.1 g, 27.5 mmol, 1.2 equiv) andTripotassium phosphate (12.0 g, 46 mmol, 2.0 equiv)Add to a mixture of 180 ml of dimethylformamide and water (5:1),Heat to 90C and react for 6 hours.Cool to room temperatureAfter suction filtration through Celite, the resulting filtrate was diluted with ethyl acetate to 1000 ml, washed with saturated brine three times, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate. Ester = 8:1 and petroleum ether: dichloromethane = 2:1),2-(1-trityl-1H-imidazol-4-yl)benzaldehyde (5.2 g, yield: 54%) was obtained as a white solid.
52%	With K3PO4;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 90℃; for 16h;Inert atmosphere;	Example 3 Suzuki Cross-Coupling of 4-Iodo-l-trityl-lH- imidazole with PhenylboronicAcids[0138] A suspension of 4-iodo-l-trytyl-lH- imidazole (6.88 mmol ), the appropriate 2-formyl boronic acid derivative (10.31 mmol) and K3PO4 (20.63 mmol) in N,N-dimethylformamide (30 mL) and water (6 mL) was purged with nitrogen for 5 minutes, followed by the addition of Pd(PPh3)4 and the mixture was purged with nitrogen for another 5 minutes. The reaction mixture was stirred at 90 C for 16 h under an atmosphere of 2.The solution was allowed to cool and was filtered through a plug of celite. The mixture was diluted with water (50 mL) and EtOAc (25 mL). The organic layer was collected and the aqueous layer was extracted with EtOAc (2 x 25 mL). The combined organic extracts were washed with water (2 x 25 mL), brine and dried ( a2S04). The solution was filtered and the solvent was removed under reduced pressure to afford the crude product which was purified by flash column chromatography on silica gel to provide the following compounds.No. Compound Name Yield (%)JH NMR(MeOH-d4) 7.16-7.27 (m, 6H), 7.29-7.47 (m, 3H), 7.60-7.70 (m, 9H), 7.85- 7.90 (m, 2H), 10.26 (s, 1H)
40.8%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 90℃; for 16h;Inert atmosphere;	4-iodo-1-trityl-1H-imidazole (38.7 g, 88.8 mmol), (2-formylphenyl)boronic acid (20.0 g, 133 mmol)And K3PO4 (56.4 g, 266 mmol) was dissolved in 1,4-dioxane (300 mL) and water (60 mL).Nitrogen gas was bubbled through the reaction solution for 5 min, then Pd(PPh3)4 (5.12 g, 4.44 mmol) was added, and the reaction mixture was bubbled with nitrogen for 5 min.The reaction was heated at 90 C for 16 h under nitrogen.After the reaction was completed, the temperature was lowered, and the celite was filtered, and the filtrate was diluted with water (100 mL) and EA (300 mL), and the mixture was allowed to stand for separation. The aqueous phase was extracted with EA (300 mL×2; combined organic phase, water (100 mL) and saturated brine (100 mL × 3) washing.The organic phase was concentrated under reduced pressure to give a residue.Purified with PE/EA=3/1 column,Obtained a light brown viscous oil 2-(1-Trityl-1H-imidazol-4-yl)benzaldehyde (15.0 g, 40.8%).
39%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 90℃;Inert atmosphere;	Compound 1 (2.2 g, 5.0mmol), o-formylphenylboronic acid(1.2 g, 7.5mmol), K3PO4 (3.2 g, 15mmol), Pd (PPh3)4 (0.6 g, 1.0mmol) is dissolved in DMF/H20 (30mL/6mL). The system is replaced with nitrogen and warmed at 90C, the reaction is stirred overnight. The reaction solution is diluted with ethyl acetate (50mL), wash with saturated brine (25mL X 3), dry over anhydrous sodium sulfate, and dry under reduced pressure. Crude column chromatography (PE: EA = 5:1), and then obtained brown solid compound 2 (810 mg, 39%).
650 mg	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 100℃;Inert atmosphere;	step 1.Take a 100ml single-mouth bottle and add 300mg 2-formylbenzeneboronic acid.1090 mg 1-trityl-4-iodoimidazole, 848 mg K3PO4,23mg Pd(PPh3)4, and 2ml water, 10ml DMF,Reacting at 100 C under N2 protection overnight,Complete reactionThe mixture was poured into water, and the mixture was extracted with EtOAc.Column chromatography gave 650 mg of light gray compound 26;

Reference： [1]Patent: CN108424415,2018,A .Location in patent: Paragraph 0219; 0220; 0221; 0222
[2]Patent: US2016/75711,2016,A1 .Location in patent: Paragraph 0251-0252
[3]European Journal of Medicinal Chemistry,2017,vol. 140,p. 293 - 304
[4]Patent: CN107501272,2017,A .Location in patent: Paragraph 0085; 0086; 0093; 0094
[5]Molecules,2019,vol. 24
[6]Patent: WO2016/131380,2016,A1 .Location in patent: Paragraph 269; 270; 271
[7]Patent: CN107383024,2017,A .Location in patent: Paragraph 0113
[8]Patent: WO2012/142237,2012,A1 .Location in patent: Page/Page column 87-88
[9]Journal of Medicinal Chemistry,2019,vol. 62,p. 6705 - 6733
[10]Patent: CN108203438,2018,A .Location in patent: Paragraph 0147; 0148; 0149; 0150
[11]Patent: CN107556315,2018,A .Location in patent: Paragraph 0051-0053
[12]Tetrahedron,2018,vol. 74,p. 3045 - 3051
[13]Patent: CN108689958,2018,A .Location in patent: Paragraph 0143-0145

54
[ 96797-15-8 ]
[ 647020-71-1 ]
[ 1402838-29-2 ]

Yield	Reaction Conditions	Operation in experiment
41%		Example 20 Meth l 3-fluoro-2-(l-trityl-lH-imidazol-4-yl)benzoate[0152] To a stirred solution of 4-iodo-l-trityl-lH- imidazole (436 mg, 1.0 mmol) in anhydrous THF (6 mL) was added EtMgBr (3.0 M in THF, 1.20 mmol, 0.40 mL) under an atmosphere of N2. The resulting solution was allowed to stir for 90 min and ZnCl2 (0.5 M in THF, 2.40 niL, 1.20 mmol) was added. The resulting white suspension was allowed to stir for 90 min and a solution of methyl 2-bromo-3-fluorobenzoate (280 mg, 1.20 mmol) in THF (1 mL) was added followed by the immediate addition of Pd(PPh3)4 (58 mg, 0.05 mmol). The reaction mixture was allowed to stir at 90 C for 18 h under an atmosphere of N2. After cooling to room temperature, the solution was diluted with CH2CI2 (20 mL) and the organic layer was washed with an EDTA (aq) buffer (pH = 9) (2 x 5 mL) and brine. The organic layer was dried ( a2S04) and concentrated under reduced pressure. The crude residue was purified by flash column chromatography to afford the desired product as yellow oil (190 mg, 41 %). H NMR: 3.93 (s, 3H), 7.12-7.59 (m, 18H), 7.56 (s, 1H), 7.73-7.75 (m, 1H).

Reference： [1]Patent: WO2012/142237,2012,A1 .Location in patent: Page/Page column 101-102

55
[ 1461-22-9 ]
[ 96797-15-8 ]
[ 208934-35-4 ]

Yield	Reaction Conditions	Operation in experiment
76%		[275] To an ice-salt bath cooling solution of 4-iodo-1-trityl-1H-imidazole (2.5 g, 5.7 mmol) in dichloromethane (DCM) (30 mL) was added ethylmagnesium bromide (2.5 mL, 7.5 mmol, 3.0 M solution in diethyl ether) slowly. The resulted mixture was stirred at roomtemperature for lh, then added chlorotributyltin (2.6 g, 8.0 mmol). The resulted mixture was stirred at room temperature for 2h, then added saturated ammonium chloride solution (50 mL), the mixture was extracted with dichloromethane (100 mLx2). The combined organic phase was washed with brine (25 mL), dried over sodium sulfate, filtered and concentrated. The residue was recrystallization with a mixed solvent (petroleum ether: ethyl acetate= 6:1) toafford 4-(tributylstannyl)-1-trityl-1H-imidazole (2.6 g, yield: 76%) as a white solid.[276] m/z: [M+H] 601
		To a solution of 4-iodo-1-(triphenylmethyl)-1H-imidazole (5 g, 11.47 mmol) in dichloromethane (75 mL) was added iPrMgBr solution (1 M in THF, 17.2 mL, 17.2 mmol) dropwise at room temperature. After stirring for additional 1 h, the reaction mixture was added by Bu3SnC1 (4.49 g, 13.76 mmol) slowly. The resulting mixture was then stirred at room temperature for 16 h. The reaction mixture was quenched by the addition of water (100 mL) carefully and the mixture was extracted with DCM (100 mL×2). The organic phases were combined, washed with brine and dried over Na2SO4. The solvent was removed under reduced pressure to yield 4-(tributylstannyl)-1-trityl-1H-imidazole as light yellow solid (6.6 g, 96% crude yield) which was used in next step without further purification. MS: m/z=601.3 [M+H]+.

Reference： [1]Patent: WO2016/131380,2016,A1 .Location in patent: Paragraph 273; 274; 275; 276
[2]Patent: US2016/75711,2016,A1 .Location in patent: Paragraph 0216; 0218

56
[ 121-43-7 ]
[ 96797-15-8 ]
(1-trityl-1H-imidazol-4-yl)boronic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%		A 2 M isopropylmagnesium chloride solution in THF (8.60 mL, 17.2 mmol) was added dropwise to a solution of 4-iodo-1-trityl-imidazole (5.00 g, 11.5 mmol) in anhydrous THF (55 mL) at 0 C under nitrogen. The resulting mixture was stirred at 0 C for 10 minutes. Trimethyl borate (6.39 mL, 57.3 mmol) was added portion wise and the reaction mixture was left to stir for 10 minutes at 0C. It was allowed to warm to room temperature and stirred for another 10 minutes. 1 M aqueoushydrochloric acid (30 mL, 30.0 mmol) was added to the reaction mixture which was stirred for 10 minutes. The reaction was quenched by slowly pouring into a saturated solution of aqueous sodium hydrogen carbonate (100 mL) and extracted with ethyl acetate (3 x 50 mL). The combined organic phases were dried over sodium sulphate, filtered and concentrated in vacuo to afford the product(1-tritylimidazol-4-yl)boronic acid (3.93 g, 11.1 mmol, 97% yield) as an off white solid which was taken through to the next synthetic step without further purification. LCMS purity >90%, 1 .42 mm (analytical short).
		To a suspension of 4-iodo-1 -trityl-imidazole (3.00g, 6.88mmol) in THF (55 ml_) at 0C was slowly added isopropylmagnesium chloride (8.6ml_, 17.19mmol), the clear solution was then left to stir for 10 minutes. Trimethyl borate (3.83ml_, 34.38mmol) was added portion wise and the reaction mixture was left to stir for 10 minutes at 0C before being allowed to reach room temperature and stir for a further 10 minutes. 1 M HCI (30 ml_) was then added and the reaction was stirred for 10 minutes. The reaction was quenched by pouring it slowly in to a saturated solution of NaHC03 solution (100 ml_) which was then extracted with EtOAc (3 x 50 ml_). The combined organic phases were then dired over Na2S04 and concentrated in vacuo to give the crude product (1 -tritylimidazol-4-yl)boronic acid (2.53g, 7.15mmol, 103.92% yield) as an off white solid. MS Method 2: RT 1 .47 min, ES+ m/z 355 [M+H]+ H NMR (400MHz, DMSO) delta/ppm: 7.20-7.45 (m, 10H), 6.95-7.10 (m, 7H).
		To a stirred solution of compound 41 (1.00 g, 2.29 mmol) in THF (15 mL) was added Isopropylmagnesium chloride , 2.0M solution in THF (1.72 mL, 3.44 mmol) dropwise at 0 C in 10 minutes under N2 atmosphere, after addition, the solution was stirred at 0 C for 15 minutes, Trimethyl borate (1.19 g, 11.46 mmol) was added at 0 C in 5 minutes, after addition, the mixture was stirred at 0 C for 15 minutes, rt for 15 minutes, then 1 M HC1 aq (10 mL) was added, stirred at rt for 10 minutes, then the mixture was poured into sat. NaHC03 aq (50 mL) slowly, extracted with EtOAc (50 ml *3), the combined organic layer was washed with brine, dried over anhydrous Na2S04, concentrate in vacuo to give compound 42 (0.90 g, 100% yield) as a crude.

Reference： [1]Patent: WO2016/59412,2016,A1 .Location in patent: Paragraph 00203
[2]Patent: WO2016/55786,2016,A1 .Location in patent: Paragraph 00232
[3]Patent: WO2018/217439,2018,A1 .Location in patent: Page/Page column 40; 41

57
[ 70201-43-3 ]
[ 96797-15-8 ]
3-(1-tritylimidazol-4-yl)pyridine-4-carbaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%		Under nitrogen, to 4-iodo-l-trit l-imidazole (2.18 g, 5.00 mmol, 1.00 equiv) in THF (10 mL) at 0 C was added z-PrMgCl (2.0 M, 2.63 mL, 5.3 mmol, 1.1 equiv). After stirring for 1.5 hr at 0 C, -Bu3SnCl (1.56 mL, 5.75 mmol, 1.15 equiv) was added and the reaction mixture was warmed to 23 C. After stirring for 20 min at 23 C, 3-bromopyridine- 4-carbaldehyde (930 mg, 5.00 mmol, 1.00 equiv), Pd(PPh3)4 (1.16 g, 1.00 mmol, 0.200 equiv), Cul (95.2 mg, 0.500 mmol, 0.100 equiv), and LiCl (2.12 g, 50.0 mmol, 10.0 equiv) were added and the reaction mixture was heated to 70 C. After stirring for 21 hr at 70 C, the reaction mixture was filtered through a pad of celite. The filtrate was concentrated in vacuo and the residue was purified by column chromatography on silica gel eluting with CH2Cl2/MeOH to afford 1.0 g of 3-(l-trityl-lH-imidazol-4-yl)isonicotinaldehyde (48% yield). [00272] NMR Spectroscopy: lH NMR (300 MHz, CDC13, 23 C, delta): 10.66 (s, 1H), 8.90 (s, 1H), 8.62 (d, J = 7.2 Hz, 1H), 7.66 (d, J = 7.2 Hz, 1H), 7.60 (s, 1H), 7.40-7.08 (m, 16H).

Reference： [1]Patent: WO2017/75341,2017,A1 .Location in patent: Paragraph 00271; 00272

58
N-(2,3-dihydro-1H-inden-2-yl)-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine [ No CAS ]
[ 96797-15-8 ]
N-(2,3-dihydro-1H-inden-2-yl)-5-[1-(triphenylmethyl)-1H-imidazol-4-yl]pyrimidin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; at 100℃; for 9h;Inert atmosphere;	The compound im-4 (0.69 g, 2.03 mmol), compound 60-a (0.68 g, 1.56 mmol) Tetrakis (triphenylphosphine) palladium (0) (0.18 g, 0.16 mmol), 2N aqueous sodium carbonate solution (2.5 mL) was dissolved in 1,4-dioxane (10 mL) Nitrogen was charged, and the mixture was stirred at 100 for 9 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, distilled water (50 mL) was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with distilled water and saturated brine, dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (ethyl acetate: n-hexane = 3: 7) to give the title compound 60-b (0.65 g, 80%) as a red solid.

Reference： [1]Patent: KR101798840,2017,B1 .Location in patent: Paragraph 1139-1140; 1145-1146

59
(5-bromo-6-fluoro-4-formylpyridin-3-yl)boronic acid [ No CAS ]
[ 96797-15-8 ]
C₂₈H₁₉BrFN₃O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	With potassium dihydrogenphosphate; tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 90℃;Inert atmosphere;	(5-Bromo-6-fluoro-4-formylpyridin-3-yl)boronic acid (1.70 g, 6.88 mmol),1-trityl-4-iodoimidazole (3.0 g, 4.59 mmol), potassium phosphate (4.38 g, 13.77 mmol),Pd(PPh3)4 (0.3 g, 10%, w/w%) was added to a mixed solution of DMF (30 mL) and water (6 mL).The system was replaced with nitrogen four times and allowed to react overnight at 90 C under nitrogen.The reaction was completely detected by TLC, cooled to room temperature, filtered, and the filtrate was diluted with ethyl acetate (300 mL).Wash three times with water (100 mL), distill the organic phase under reduced pressure, and the residue was purified by flash column chromatography.The target product was 1.57 g, and the yield was 67%.

Reference： [1]Patent: CN108424414,2018,A .Location in patent: Paragraph 0215-0218

60
[ 871126-22-6 ]
[ 96797-15-8 ]
C₂₉H₂₁FN₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
520 mg	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 100℃;Inert atmosphere;	Take a 100ml single-mouth bottle,Add 335 mg of <strong>[871126-22-6]2-fluoro-4-formylbenzeneboronic acid</strong>,1144 mg of 1-trityl-4-iodoimidazole,848mg K3PO4, 23mg Pd(PPh3)4,And 2ml of water, 10ml DMF,The reaction was carried out at 100 C under N2 overnight, and the reaction was completely lowered to room temperature.It was poured into water and extracted with EA. The organic phase was washed with saturated NaCI solution and dried over anhydrous NaSO4, Column chromatography gave light gray 520 mg of compound 13-1, which was used;

Reference： [1]Patent: CN108689958,2018,A .Location in patent: Paragraph 0100; 0101; 0103

61
[ 871126-22-6 ]
[ 96797-15-8 ]
C₃₉H₂₆F₂N₈O₃ [ No CAS ]

Reference： [1]Patent: CN108689958,2018,A

62
[ 1009307-13-4 ]
[ 96797-15-8 ]
[ 111157-50-7 ]

Yield	Reaction Conditions	Operation in experiment
2 g	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 6h;	A mixture of 4-iodo-1-(triphenylmethyl)-1H-imidazole (7.41 g, 16.98 mmol), ethyl (2E)-3-(tetramethyl-1,3,2-dioxaborolan-2-yl)prop-2-enoate (9.60 g, 42.46 mmol), tetrakis(triphenylphosphine)palladium (1.96 g, 1.69 mmol,), potassium phosphate (10.82 g, 50.97 mmol) in 1,4-dioxane (100 mL) and water (20 mL) was stirred for 6 h at 100 C. The reaction was concentrated under vacuum. The residue was purified by silica gel column with ethyl acetate/petroleum ether (20/80) to afford ethyl (2E)-3-[1-(triphenylmethyl)-1H-imidazol-4-yl]prop-2-enoate(2 g, 4.90 mmol) as a light yellow solid. LCMS (ESI) [M+H]+=409.

Reference： [1]Patent: US2018/282282,2018,A1 .Location in patent: Paragraph 2346; 2347

63
[ 1009307-13-4 ]
[ 96797-15-8 ]
ethyl trans-2-[1-(triphenylmethyl)-1H-imidazol-4-yl]cyclopropane-1-carboxylate [ No CAS ]

Reference： [1]Patent: US2018/282282,2018,A1

64
[ 96797-15-8 ]
[ 139962-95-1 ]
C₃₀H₂₄N₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; tetrakis(triphenylphosphine) palladium⁽⁰⁾ In N,N-dimethyl-formamide at 100℃; Inert atmosphere;	Preparation of 4-(2-methoxyphenyl)-1-trityl-1H-imidazole (6) General procedure: 4-Iodo-1-trityl-1H-imidazole (5, 2 g, 4.58 mmol), (5-chloro-2-methoxyphenyl)boronic acid(0.852 g, 4.58 mmol), K3PO4 (2.9 g, 13.7 mmol), Pd(PPh3)4 (0.74 g, 0.64 mmol) were added todry dimethylformamide (30 mL). The reaction mixture was stirred at 100 °C under inert atmosphere,until the starting material disappeared in TLC. The reaction mixture was distilled in vacuo, and ethylacetate (100 mL) was added to the mixture. The organic extract was washed twice with saturatedaqueous NaCl (20 mL), and the organic extract was dried over Na2SO4. After solvent was removedunder vacuum, the product was purified as a white solid by silica gel column chromatography, 1.2 g,yield 63%.

Reference： [1]Wen, Hui; Liu, Yuke; Wang, Shufang; Wang, Ting; Zhang, Gang; Chen, Xiaoguang; Li, Yan; Cui, Huaqing; Lai, Fangfang; Sheng, Li [Molecules, 2019, vol. 24, # 11]

65
[ 5720-06-9 ]
[ 96797-15-8 ]
4-(2-methoxyphenyl)-1-trityl-1H-imidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 100℃;Inert atmosphere;	<strong>[96797-15-8]4-Iodo-1-trityl-1H-imidazole</strong> (5, 2 g, 4.58 mmol), (5-chloro-2-methoxyphenyl)boronic acid(0.852 g, 4.58 mmol), K3PO4 (2.9 g, 13.7 mmol), Pd(PPh3)4 (0.74 g, 0.64 mmol) were added todry dimethylformamide (30 mL). The reaction mixture was stirred at 100 C under inert atmosphere,until the starting material disappeared in TLC. The reaction mixture was distilled in vacuo, and ethylacetate (100 mL) was added to the mixture. The organic extract was washed twice with saturatedaqueous NaCl (20 mL), and the organic extract was dried over Na2SO4. After solvent was removedunder vacuum, the product was purified as a white solid by silica gel column chromatography, 1.2 g,yield 63%. 1H-NMR (400 MHz, CDCl3): = 7.51-7.32 (m, 12H, H-phenyl, H-imidazolyl), 7.15-7.04 (m,8H, H-phenyl, H-imidazolyl), 6.94 (d, J = 8.1 Hz, 1H, H-phenyl), 3.99 (s, 3H, CH3). HRMS (ESI): m/z[M + H]+ calculated for C29H25N2O: 417.19614; found: 417.19647.

Reference： [1]Molecules,2019,vol. 24

66
[ 1256355-30-2 ]
[ 96797-15-8 ]
[ 1402838-12-3 ]

Reference： [1]Journal of Medicinal Chemistry,2019,vol. 62,p. 6705 - 6733

67
[ 825644-26-6 ]
[ 96797-15-8 ]
5-fluoro-2-(1-trityl-1H-imidazol-4-yl)benzaldehyde [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2019,vol. 62,p. 6705 - 6733

68
[ 96797-15-8 ]
[ 60290-21-3 ]
C₂₉H₂₁ClN₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%		Cul (21.8 mg, 0.12 mmol), /nmv-N,N'-dimcthylcyclohcxanc- 1 ,2-diaminc (36.1 iiL, 0.23 mmol) and K2CO3 (317 mg, 2.29 mmol) were added to a solution of 1-169 (500 mg, 1.15 mmol) in toluene (6.25 mL) in a sealed tube while N2 was bubbling. After 10 min, 4-chloro-lH-pyrrolo[3,2-c]pyridine [60290-21-3] (227 mg, 1.15 mmol) was added. The reaction mixture was stirred at room temperature for 10 min, and at 100 C for 20 h. The reaction mixture was cooled to room temperature and diluted with NaHCCh (sat., aq.) and extracted with EtOAc. The organic layer was dried (MgS04), filtered and the solvents were evaporated in vacuo. The crude mixture was purified by flash column chromatography (silica, heptane/EtOAc, gradient from 100:0 to 80:20) to afford 1-170 (430 mg, 81%).

Reference： [1]Patent: WO2019/243535,2019,A1 .Location in patent: Page/Page column 87

69
[ 363185-87-9 ]
[ 96797-15-8 ]
C₃₀H₂₅N₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In water; ethyl acetate; toluene at 120℃; for 1.66667h; Inert atmosphere; Sealed tube;	D Synthetic procedure D: Synthesis of methyl heterorarylanthranilate 5. Methyl 4(or 5)-pinacolboranylanthranilate (Compound 1 in Scheme 3a, 0.416 g, 1.5 mmol) was mixed with heteroarylbromide or heteroaryliodide (Compound 2 in Scheme 3a with X = Br or I, 1 mmol) in a mixture of ethyl acetate (10 ml_) and toluene (20 ml_). PdCl2(PPh3)2 (0.070 g, 0.1 mmol) was added followed by aqueous sodium carbonate (4 ml_, 2N). The reaction mixture was purged with nitrogen and the reaction vessel sealed and heated at 120°C for 100 minutes. The cooled mixture was poured into water and the organic layer was washed with brine, dried and evaporated to dryness to afford the title compound methyl 4(or 5)- heterorarylanthranilate (Compound 3 in Scheme 3a). The material was used in the following step without further purification.

Reference： [1]Current Patent Assignee: GERO DISCOVERY - WO2020/80979, 2020, A1 Location in patent: Page/Page column 130; 151

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Aryls

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