51746-85-1|3-(1H-Imidazol-5-yl)pyridine| Ambeed

CAS No. :	51746-85-1
Formula :	C₈H₇N₃
M.W :	145.16
SMILES Code :	C1(C2=CNC=N2)=CC=CN=C1
MDL No. :	MFCD10565593
InChI Key :	YFOKBFRTGLSZLU-UHFFFAOYSA-N
Pubchem ID :	3040177

Safety of [ 51746-85-1 ]

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

Application In Synthesis of [ 51746-85-1 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 51746-85-1 ]

[ 51746-85-1 ] Synthesis Path-Downstream 1~54

1
[ 859076-83-8 ]
[ 51746-85-1 ]

References: [1]Chemische Berichte,1936,vol. 69,p. 1147,1148.
Yakugaku Zasshi,1936,vol. 56,p. 525,528.

2
[ 51746-85-1 ]
3-(1⁽³⁾H-imidazol-4-yl)-piperidine [ No CAS ]

References: [1]Chemische Berichte,1936,vol. 69,p. 1147,1148.
Yakugaku Zasshi,1936,vol. 56,p. 525,528.

3
[ 5394-18-3 ]
[ 51746-85-1 ]
[ 173838-67-0 ]

References: [1]Journal of Asian Natural Products Research,2018,p. 1 - 9.
[2]Bioorganic and Medicinal Chemistry Letters,1999,vol. 9,p. 3075 - 3080.
[3]Patent: US2005/14706,2005,A1 .Location in patent: Page/Page column 8.

5
[ 51746-85-1 ]
[ 251354-75-3 ]
5-methyl-1H-pyrrole-2-carboxylic acid 5-hydroxy-3-methoxy-2,2-dimethyl-6-{8-methyl-2-oxo-4-[2-(4-pyridin-3-yl-imidazol-1-yl)-ethoxy]-2H-chromen-7-yloxy}-tetrahydro-pyran-4-yl ester [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,1999,vol. 9,p. 2875 - 2880.

6
[ 2302-25-2 ]
[ 1692-25-7 ]
[ 51746-85-1 ]

References: [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 224 - 239.

7
[ 96-49-1 ]
[ 51746-85-1 ]
[ 401522-20-1 ]

References: [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 3503 - 3519.

8
[ 51746-85-1 ]
[ 100-39-0 ]
3-(1-benzyl-1H-imidazol-4-yl)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%		[0338] 3-benzyl-lH-imidazol-4-ylpyridine (60). To a solution of 34 (35 mg, 0.25 mmol) in THF (5 mL) under argon was added sodium hydride (12 mg, 0.29 mmol) in one portion and the resultant slurry was stirred for 20 min. Benzyl bromide (26 uL, 0.32 mmol) was added and the resultant solution was stirred for 10 min. The reaction was quenched by the slow addition of HCl (aq) (1 N, 2 mL), diluted with 13 mL of water and washed with ethyl acetate (3 x 15 ml). Dichloromethane was added (25 mL) and the aqueous fraction was adjusted to pH 9 with NaOH (aq) (10 N). The organic fraction was collected and the aqueous was extracted with dichloromethane (20 mL), the combined organic fractions were dried (Na2S04), filtered and the solvent was removed in vacuo. The crude material was chromatographed on silica gel (CH30H/CHC13, 2.5/97. 5, Rf= 0.26) to afford the title compound 60 (43 mg, 74% yield) as a white semisolid : 1H NMR (CDC13) 8 8.95 (br s, 1H), 8.47 (br s, 1H), 8.10 (m, 1H) 7.64 (m, 1H) 7.42-7. 17 (m, 7H) 5.17 (s, 2H); LRMS (ESI) nilz calcd for C15Hl4N3 [M + H]+ 236, found 236; HRMS (ESI) nilz calcd for C15Hl4N3 [M + H] + 236.1188, found 236.1198 ; HPLC > 99% (tR = 10 min, 60 (A): 40 (B): 0. 02 (C); tR = 6. 12 min, 60 (A): 40 (B): 0. 07 (C)).

References: [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 224 - 239.
[2]Patent: WO2005/66162,2005,A1 .Location in patent: Page/Page column 111.

9
[ 51746-85-1 ]
[ 75-03-6 ]
3-(1-ethyl-1H-imidazol-4-yl)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%		[0337] 3-Ethyl-lH-imidazol-4-yl) pyridine (59). To a solution of 34 (36 mg, 0.25 mmol) in THF (5 mL) under argon was added sodium hydride (12 mg, 0.29 mmol) in one portion and the resultant slurry was stirred for 20 min. Iodoethane (26 pL, 0. 32 mmol) was added and the resultant solution was stirred for 10 min. The reaction was stopped by the careful addition of aqueous hydrochloric acid (1 N, 2 mL), diluted with 13 mL of water and washed with ethyl acetate (3 x 15 ml). Dichloromethane was added (25 mL) and the aqueous was adjusted to pH 9 with NaOH (aq) (10 N). The organic fraction was collected and the aqueous fraction was extracted with dichloromethane (20 mL), the combined organic fractions were dried Na2SO4), filtered and the solvent was removed in vacuo. The crude material was chromatographed on silica gel (CH30H/CHC13, 2.5/97. 5, Rf= 0.27) to afford the title compound 59 (34 mg, 79% yield) as a clear oil :'H NMR (CDCl3) 5 8.93 (m, 1H), 8.44 (m, 1H), 8.07 (m, 1H), 7.54 (br s, 1H), 7.28 (m, 2H), 4.02 (q, J= 7.4 Hz, 2H), 1.49 (t, J= 7.4 Hz, 3H); LRMS (ESI) m/z calcd for GioHnNs [M + H] + 174, found 174; HRMS (ESI) mlz calcd for CloHllN3 [M + H] + 174. 1031, found 174.1042 ; HPLC > 97% (tR = 13. 28 min, 60 (A): 40 (B): 0.02 (C); tR= 3. 67 min, 80 (A): 20 (B): 0. 1 (C).

References: [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 224 - 239.
[2]Patent: WO2005/66162,2005,A1 .Location in patent: Page/Page column 111.

10
[ 51746-85-1 ]
[ 74-88-4 ]
3-(1-methyl-1H-imidazol-4-yl)pyridine [ No CAS ]
[ 859239-29-5 ]

Yield	Reaction Conditions	Operation in experiment
		[0336] 3- (1-Methyl-LH-imidazol-4-yl) pyridine and 3- (1-methyl-1H imidazol-5- yl) pyridine (58a, b). To a solution of 34 (37 mg, 0.26 mmol) in THF (4 mL) under argon was added sodium hydride (11 mg, 0.28 mmol) in one portion and the resultant slurry was stirred for 5 min. Iodomethane (190 pL, 0.31 mmol) was added and the resultant solution was stirred for 10 min. The reaction was stopped by the careful addition of aqueous hydrochloric acid (0.25 N, 6 mL) and washed with ethyl ether (3 x 10 ml). The aqueous fraction was adjusted to pH 9 with NaOH (aq) (10 N) and extracted with ethyl ether (3 x 30 mL), dried (Na2SO4), filtered and the solvent was removed in vacuo. The crude material was chromatographed on silica gel (CH30H/CHCl3, 2.5/97. 5, Rf= 0.15) to afford the title compounds 58a, b as an inseparable mixture (27 mg, 66% yield) of an orange oil: 58a 1H NMR (CDC13) 8 8.95 (m, 1H), 8.47 (m, 1H), 8.11 (m, 1H), 7.52 (br s, 1H), 7.31 (m, 1H), 7.26 (br s, 1H) 3.75 (s, 3H); 58b 1H NMR (CDCl3) 8 8.69 (m, 1H), 8.62 (m, 1H), 7.71 (m, 1H), 7.62 (br s, 1H), 7.39 (m, 1H), 7.19 (br s, 1H), 3.70 (s, 3H); LRMS (ESI) m/z calcd for CgHioNs [M + H] + 160, found 160; HRMS (ESI) m/z calcd forCgHsoN3 [M + H] + 160. 0875, found 160.0866 ; HPLC > 99% (tR = 19.80 min, 55 (A): 45 (B): 0.032 (C); tR = 9.47 min, 55 (A): 45 (B): 0.1 (C).

References: [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 224 - 239.
[2]Patent: WO2005/66162,2005,A1 .Location in patent: Page/Page column 110.

11
[ 5460-29-7 ]
[ 51746-85-1 ]
[ 892860-06-9 ]

References: [1]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 3697 - 3711.

12
[ 5292-43-3 ]
[ 51746-85-1 ]
[ 568629-89-0 ]

Yield	Reaction Conditions	Operation in experiment
	With NaH; trifluoroacetic acid; In N-methyl-acetamide; dichloromethane; water;	EXAMPLE 90 Preparation of 4-(3-pyridyl)imidazol-1-ylacetic Acid To a solution of 55 mg of 4-(3-pyridyl)imidazole (0.38 mmol, 1.0 eq.) in 2 ml of dry of dimethylformamide was added 15.5 mg of NaH (60%) (0.38 mmol, 1.0 eq.), and the mixture was stirred vigorously for 10 min. before dropwise addition of 0.05 ml of tert-butyl bromoacetate (0.34 mmol, 0.9 eq.). The resulting solution was heated at 70 C. for 30 min before it was diluted with 20 ml of water, and extracted with 3*30 ml of ethyl acetate. The organic extracts were combined and washed sequentially with water, and brine. The organic phase was dried with MgSO4, filtered, and evaporated to give 60 mg of a slight yellow solid. To a solution of above solid in 5 ml of CH2Cl2 was added 5 ml of trifluoroacetic acid, and the resulting solution was stirred at room temperature for 3 h. The solvent was then evaporated under vacuum to give 35 mg of final productproduct.

References: [1]Patent: US6939861,2005,B2 .

13
[ 51746-85-1 ]
[ 325478-13-5 ]

References: [1]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 3697 - 3711.

14
[ 51746-85-1 ]
C₄₅H₆₈N₆O₁₂ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 3697 - 3711.

15
[ 51746-85-1 ]
C₄₄H₆₆N₆O₁₂ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 3697 - 3711.

16
[ 51746-85-1 ]
[ 892860-49-0 ]

References: [1]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 3697 - 3711.

17
[ 626-55-1 ]
K₄[Fe(CN)6] [ No CAS ]
[ 51746-85-1 ]

References: [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 224 - 239.

18
[ 51746-85-1 ]
[ 401522-23-4 ]

References: [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 3503 - 3519.

19
[ 51746-85-1 ]
[ 401522-21-2 ]

References: [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 3503 - 3519.

20
[ 51746-85-1 ]
[ 401522-22-3 ]

References: [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 3503 - 3519.

21
[ 51746-85-1 ]
9-(4-dimethylamino-3-hydroxy-6-methyl-tetrahydro-pyran-2-yloxy)-15-ethyl-8-methoxy-4,6,8,10,12,15a-hexamethyl-3-[2-(4-pyridin-3-yl-imidazol-1-yl)-ethylsulfanyl]-octahydro-1,14-dioxa-cyclopentacyclotetradecene-2,5,11,13-tetraone [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 3503 - 3519.

22
[ 51746-85-1 ]
C₄₄H₆₆N₄O₁₁S [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 3503 - 3519.

23
[ 51746-85-1 ]
C₄₄H₆₄N₄O₁₁S [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 3503 - 3519.

24
[ 51746-85-1 ]
C₆₀H₈₆N₄O₁₆S [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 3503 - 3519.

25
[ 51746-85-1 ]
[ 401522-24-5 ]

References: [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 3503 - 3519.

26
[ 51746-85-1 ]
[ 191114-48-4 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,1999,vol. 9,p. 3075 - 3080.

27
[ 51746-85-1 ]
[ 173838-63-6 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,1999,vol. 9,p. 3075 - 3080.
[2]Journal of Asian Natural Products Research,2018,p. 1 - 9.

28
[ 857797-77-4 ]
[ 51746-85-1 ]

References: [1]Chemische Berichte,1936,vol. 69,p. 1147,1148.
Yakugaku Zasshi,1936,vol. 56,p. 525,528.

29
[ 857812-29-4 ]
[ 51746-85-1 ]

References: [1]Chemische Berichte,1936,vol. 69,p. 1147,1148.
Yakugaku Zasshi,1936,vol. 56,p. 525,528.

30
[ 107-86-8 ]
[ 51746-85-1 ]
[ 261765-52-0 ]

Yield	Reaction Conditions	Operation in experiment
	With acetic acid; In tetrahydrofuran; for 24h;Heating / reflux;	To a solution of 4-pyridin-3-yl-imidazole (1 g) in THF (34 ML) was added acetic acid (1.6 ML) and 3-methyl-2-butenal (3.3 ML) and the resulting solution was heated under gentle reflux for 24 hours. THF was then removed in vacuo and the residue was purified on a Flash 75 long column eluding with MeOH-CH2Cl2 to give the title compound as slightly yellow oil. MS: m/z 230 (M+H).
	With acetic acid; In tetrahydrofuran;	EXAMPLE 15 3,3-Dimethyl-3(4-Pyridin-3-yl-imidazol-1-yl)-propioaldehyde To a solution of 4-pyridin-3-yl-imidazole (1 g) in THF (34 mL) was added acetic acid (1.6 mL) and 3-methyl-2-butenal (3.3 mL) and the resulting solution was heated under gentle reflux for 24 hours. THF was then removed in vacuo and the residue was purified on a Flash 75 (silica gel column made by Biotage Division of Dyax Corp, U.S.) long column eluding with MeOH-CH2Cl2 to give the title compound as slightly yellow oil. MS: m/z 230 (M+H).
	With acetic acid; In tetrahydrofuran;	Example 15 3,3-Dimethyl-3-(4-pyridin-3-yl-imidazol-1-yl)-propioaldehyde To a solution of 4-pyridin-3-yl-imidazole (1 g) in THF (34 mL) was added acetic acid (1.6 mL) and 3-methyl-2-butenal (3.3 mL) and the resulting solution was heated under gentle reflux for 24 hours. THF was then removed in vacuoand the residue was purified on a Flash 75 long column eluding with MeOH-CH2Cl2to give the title compound as slightly yellow oil. MS: m/z 230 (M+H).

References: [1]Patent: US6664238,2003,B1 .Location in patent: Page column 26.
[2]Patent: US6420343,2002,B1 .
[3]Patent: EP1298138,2003,A1 .

31
[ 78-85-3 ]
[ 51746-85-1 ]
[ 271795-48-3 ]

Yield	Reaction Conditions	Operation in experiment
	With acetic acid; In tetrahydrofuran; for 48h;Heating / reflux;	2-Methyl-3-(4-pyridin-3-yl-imidazol-1-yl)-propioaldehyde To a solution of 4-pyridin-3-yl-imidazole (8.5 g) in THF (tetrahydrofuran) (293 ML) was added acetic acid (16.8 ML) and methacrolein (9.7 ML) and the resulting solution was heated under gentle reflux for 24 hours.. Another 9.7 ML methacrolein was added and the solution was heated under reflux for another 24 hours. THF was then removed in vacuo and the residue was purified on a Flash 75 long column eluding with MeOH-CH2Cl2 to give the title compound as slightly yellow oil. MS: m/z 215 (M+H).
	With acetic acid; In tetrahydrofuran;	Example 14 2-Methyl-3-(4-pyridin-3-yl-imidazol-1-yl)-propioaldehyde To a solution of 4-pyridin-3-yl-imidazole (8.5 g) in THF (tetrahydrofuran) (293 mL) was added acetic acid (16.8 mL) and methacrolein (9.7 mL) and the resulting solution was heated under gentle reflux for 24 hours. Another 9.7 mL methacrolein was added and the solution was heated under reflux for another 24 hours. THF was then removed in vacuo and the residue was purified on a Flash 75 long column eluding with MeOH-CH2Cl2to give the title compound as slightly yellow oil. MS: m/z 215 (M+H).
	With acetic acid; In tetrahydrofuran;	Example 21 2-Methyl-3-(4-pyridin-3-yl-imidazol-1-yl)-propioaldehyde To a solution of 4-pyridin-3-yl-imidazole (8.5 g) in THF (293 mL) was added acetic acid (16.8 mL) and methacrolein (9.7 mL) and the resulting solution was heated under gentle reflux for 24 hours. Another 9.7 mL methacrolein was added and the solution was heated under reflux for another 24 hours. THF was then removed in vacuoand the residue was purified on a Flash 75 long column eluding with MeOH-CH2Cl2to give the title compound as slightly yellow oil. MS: m/z 215 (M+H).

References: [1]Patent: US6664238,2003,B1 .Location in patent: Page column 26; 28.
[2]Patent: EP1298138,2003,A1 .
[3]Patent: EP1298138,2003,A1 .

32
[ 3492-41-9 ]
[ 51746-85-1 ]
[ 271795-49-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; In dimethyl sulfoxide; at 70℃; for 48h;	To a solution of 4-pyridin-3-yl-imidazole (50 mg) in DMSO (methyl sulfoxide) (1.7 ML) was added powered KOH (57 mg) and 3-bromo-2,2-dimethylpropyl acetate and the resulting suspension was heated at 70 C. for 48 hours.. water was added followed by CHCl3, the aqueous layer was extracted with CHCl3, the combined organic layers were washed with brine, dired over Na2SO4 and evaporated in vacuo.. The redisue was purified by preparative TLC (10% MeOH-90% CH2Cl2) the title compound as slightly yellow oil. MS: m/z 274 (M+H).

References: [1]Patent: US6664238,2003,B1 .Location in patent: Page column 26; 28-29.

33
C₂H₂O₄*C₈H₇N₃ [ No CAS ]
[ 51746-85-1 ]

References: [1]Patent: US6353108,2002,B1 .Location in patent: Page column 4.

34
[ 254430-69-8 ]
[ 77287-34-4 ]
[ 51746-85-1 ]

Yield	Reaction Conditions	Operation in experiment
51%	at 20 - 80℃; for 21h;	Stage A2: 4-(3-pyridinyl)-1Himidazole 7.2 g of beta,beta-dimethoxy-3-pyridineethanamine in 15 ml of formamide is heated for 5 hours at 80 C. under nitrogen.. The reaction mixture is maintained under agitation at 20 C. for 16 hours.. In this way the sought product is obtained. (Yield=51%). NMR CDCl3 ppm3.24(s) 3.26(s) 6H 2 CH3O3.55(d, s after exch.) CH2-NHCO3.75(d, s after exch.) CH2-NHCO5.80(m) mobile H

References: [1]Patent: US6353108,2002,B1 .Location in patent: Page column 3-4.

35
[ 51746-85-1 ]
[ 109-64-8 ]
3-[1-(3-bromopropyl)-1H-imidazol-4-yl]-pyridine [ No CAS ]

References: [1]Patent: US2005/14706,2005,A1 .Location in patent: Page/Page column 13.

36
[ 100-54-9 ]
[ 30718-17-3 ]
[ 51746-85-1 ]

Yield	Reaction Conditions	Operation in experiment
		In accordance with the procedure of Example 3, 3-cyanopyridine is reacted with trimethylsilylmethyl isocyanide to yield 4(5)-(3-pyridyl)imidazole.

References: [1]Patent: US2005/101785,2005,A1 .Location in patent: Page/Page column 6.

37
[ 484673-02-1 ]
[ 51746-85-1 ]
[ 107-02-8 ]
C₆₄H₈₃F₃N₆O₁₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With acetic acid; at 20℃; for 2h;	To carbazate 209 in glacial acetic acid (0.05 M) was added 4- (3- PYRIDYL) -IMIDAZOLE (8 EQ) AND ACROLEIN (1.2 EQ) AT ROOM TEMPERATURE. AFTER 2 HOURS, the reaction was quenched with NAHC03 (sat. ), the imine extracted with EtOAc, and concentrated under reduced pressure. The crude intermediate was dissolved in MeOH (0.02 M), 2 drops of HOAc was added, followed by NaCNBH3 (10 eq), and the reaction mixture was stirred for 8 h at room temperature. The reaction was quenched with NAHC03 (sat. ), diluted with EtOAc, separated, and the organic layer was washed with brine. The crude carbazate product 210b was taken on to the next step without further purification. LCMS (ES); Mass found [ (M+2H)/2] =618.6 ; Exact mass for C64H87F3N6015 2+ [ (M+2H)/21=618. 70

References: [1]Patent: WO2004/96822,2004,A2 .Location in patent: Page 215.

38
[ 484673-34-9 ]
[ 51746-85-1 ]
[ 107-02-8 ]
[ 484673-35-0 ]

Yield	Reaction Conditions	Operation in experiment
		Compound 18 of Example 67 (1.00 eq) was dissolved in DMF. Hydrazine hydrate (4.0 eq) was added. The solution was stirred at ambient temperature for 3 h. The reaction mixture was poured into EtOAc and washed sequentially with water and brine. The organic layer was dried over NA2SO4, filtered, and concentrated. Column chromatography (5: 2 hexanes: EtOAc + 2% Et3N) gave the cyclic carbazide 77, ES/MS m/z 360 [(M+2H+)/2], C37H55N3O11 = 718 g/mol. [00371] The cyclic carbazate 77 (1.0 eq) and 4- (3-PYRIDYL)-IMIDAZOLE (3.0 eq) was dissolved in HOAc. Freshly distilled acrolein (1.2 eq) was added. The solution was stirred at ambient temperature for 16 h; and sodium triacetoxyborohydride (8. 0 eq) was added. The solution was stirred for an additional 8.5 h. The reaction mixture was poured into EtOAc and quenched by the addition of 6 N aqueous sodium hydroxide and saturated aqueous sodium bicarbonate. The layers were separated; and the organic layer was washed with brine then dried over NA2S04, filtered, and concentrated. Column chromatography (2: 1 hexanes : acetone + 2% Et3N to 1: 2 hexanes: acetone + 2% ET3N) gave 78. ES/MS M/Z 452 [ (M+2W)/21, C48H66N6011 903 g/mol. [00372] A 0. 05 M solution of 78 in methanol was refluxed for 15 h. The mixture was brought to ambient temperature and concentrated. Column chromatography (94: 5: 1 CHCI3 : MeOH: NH40H) gave 79. ES/MS M/Z 400 [(M+2H+)/Q, C41H62N6010 = 799 G/MOL.

References: [1]Patent: WO2004/96822,2004,A2 .Location in patent: Page 225; 226.

39
[ 63464-84-6 ]
[ 51746-85-1 ]

Yield	Reaction Conditions	Operation in experiment
	With formaldehyd; ammonia; In water; dimethyl sulfoxide; at -3 - 30℃;	Example 3 Synthesis of 3-(4-Imidazolyl)pyridine 3-(Dibromoacetyl)pyridine hydrobromide (3.00 g, 8.34 mmol) and DMSO (6 ml) were added in a reaction vessel and the mixture was stirred at 33-36 C. for 4 hr. As a result of the confirmation by HPLC, an area percentage of (3-pyridyl)glyoxal was 33.8%. After cooling to 20 C., Na2CO3 (0.44 g, 4.2 mmol) was added and the mixture was stirred at room temperature for 2 days (the reaction mixture A). As a result of the HPLC analysis, an area percentage of (3-pyridyl)glyoxal was 71.2%. Separately, formaldehyde (6.77 g, 0.083 mol) was added dropwise 28% aqueous ammonia (15.21 g, 0.25 mol) under ice-cooling at not more than 10 C. to prepare reaction mixture B. The reaction mixture A was diluted with H2O (4 ml) and the dilute reaction mixture A was added dropwise to the reaction mixture B at -3 to 2 C. The mixture was stirred overnight at 20-30 C. to give 3-(4-imidazolyl)pyridine. From the LC analysis, the yield thereof was 59.3%. 1H-NMR(400 MHz, CDCl3) delta 8.99 (d, J=2.0 Hz, 1H), 8.43(dd, J=4.9, 1.5 Hz, 1H), 8.05(dt, J=8.3, 2.0 Hz, 1H), 7.77(d, J=1.0 Hz, 1H), 7.43(d, J=1.0 Hz, 1H), 7.29(dd, J=7.8, 4.9 Hz, 1H). melting point: 117.0-118.3 C.

References: [1]Patent: US6649768,2003,B1 .Location in patent: Page/Page column 7.

40
[ 51746-85-1 ]
[ 1055345-99-7 ]

Yield	Reaction Conditions	Operation in experiment
		Step 8a. 1-(3-butenyl)-4-(3-pyridyl)-imidazole; The title compound is produced according to the procedure described in step 7a except substituting 4-(3-pyridyl)-imidazole for 4-phenylimidazole.

References: [1]Patent: US2003/114395,2003,A1 .

41
[ 600-00-0 ]
[ 96042-30-7 ]
[ 51746-85-1 ]
[ 484673-55-4 ]

Yield	Reaction Conditions	Operation in experiment
33%	With triethanolamine; potassium carbonate; In methanol; N,N-dimethyl-formamide;	EXAMPLE 92(l) Synthesis of 2-Methyl-2-(4-pyridin-3-yl-imidazol-1-yl)-propionic acid ethyl ester To a solution of 3-(1H-Imidazol-4-yl)-pyridine (1 eq) in DMF was added potassium carbonate (2 eq) under dry condition. After stirring for 1 hour, ethyl 2-bromoisobutyrate (5 eq) was added to the mixture. The solution was left stirring over 36 hours at room temperature. The reaction solvent was removed in vacuo and the solid was diluted with ethyl acetate washed with H2O, NaCl(sat), dried over sodium sulfate, filtered and concentrated. The crude product was purified by flash chromatography using a solvent gradient of 97% DCM, 3% MeOH and 0.1% TEA to yield 2-Methyl-2-(4-pyridin-3-yl-imidazol-1-yl)-propionic acid ethyl ester (33%). MH+(260)

References: [1]Patent: US2003/125266,2003,A1 .

42
[ 624-28-2 ]
[ 51746-85-1 ]
[ 883230-74-8 ]

Yield	Reaction Conditions	Operation in experiment
	In 1-methyl-pyrrolidin-2-one; for 8h;Heating / reflux;	To a solution of 2,5-dibromopyridine (1 g) in N-methylpyrrolidine-2-one (10 mL) was added 3-(lH-imidazol-4yl)-pyridine and the reaction mixture was stirred for 8 hours at reflux temperature. The reaction mixture was cooled to room temperature, poured into water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and concentrated to form a thick emulsion. The emulsion was dissolved in methanol and treated with water to separate out solid product, which was filtered and dried to yield the title compound (615 mg).EIMS (m/z): 301.11 (M+H)

References: [1]Patent: WO2006/38100,2006,A1 .Location in patent: Page/Page column 73.

43
[ 51746-85-1 ]
[ 271795-49-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; In DMSO (methyl sulfoxide); chloroform; water;	Example 15 2,2-Dimethyl-3-(4-pyridin-3-yl-imidazol-1-yl)-propyl acetate To a solution of 4-pyridin-3-yl-imidazole (50 mg) in DMSO (methyl sulfoxide) (1.7 mL) was added powered KOH (57 mg) and 3-bromo-2,2-dimethylpropyl acetate and the resulting suspension was heated at 70C for 48 hours. Water was added followed by CHCl3, the aqueous layer was extracted with CHCl3, the combined organic layers were washed with brine, dired over Na2SO4and evaporated in vacuo. The redisue was purified by preparative TLC (10% MeOH-90% CH2Cl2) the title compound as slightly yellow oil. MS: m/z 274 (M+H).
	With potassium hydroxide; In chloroform; water; dimethyl sulfoxide;	Example 22 2,2-Dimethyl-3-(4-pyridin-3-yl-imidazol-1-yl)-propyl acetate To a solution of 4-pyridin-3-yl-imidazole (50 mg) in DMSO (1.7 mL) was added powered KOH (57 mg) and 3-bromo-2,2-dimethylpropyl acetate and the resulting suspension was heated at 70C for 48 hours. Water was added followed by CHCl3, the aqueous layer was extracted with CHCl3, the combined organic layers were washed with brine, dired over Na2SO4and evaporated in vacuo. The residue was purified by preparative TLC (10% MeOH-90% CH2Cl2) the title compound as slightly yellow oil. MS: m/z 274 (M+H).

References: [1]Patent: EP1298138,2003,A1 .
[2]Patent: EP1298138,2003,A1 .

44
[ 1029684-39-6 ]
[ 51746-85-1 ]

References: [1]Tetrahedron,2008,vol. 64,p. 4596 - 4601.

45
[ 51746-85-1 ]
[ 106-96-7 ]
[ 1087353-81-8 ]

Yield	Reaction Conditions	Operation in experiment
47%	With sodium hydride; In tetrahydrofuran; at 0 - 20℃; for 3h;	To a solution of 3-(lH-Imidazol-4-yl)-pyridine (750 mg, 5.17 mmol) in THF was added NaH (310mg, 7.76 mmol) followed by the addition of propargyl bromide (1.35 mL, 15.51 mmol) at 0 <n="83"/>3C and the resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was first quenched with water and then extracted with ethyl acetate, washed with water and brine. The combined organic layers were dried over Na2SO4 and the concentrated under vacuum to yield crude product (450 mg) that was directly taken for further step.Yield: 47%ES-MS (m/z): 184 (M++1)

References: [1]Patent: WO2008/143649,2008,A2 .Location in patent: Page/Page column 81-82.

46
[ 5292-43-3 ]
[ 51746-85-1 ]
[ 1412456-67-7 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 90; Preparation of 4-(3-pyridyl)imidazol-1-ylacetic Acid [0428] To a solution of 55 mg of 4-(3-pyridyl)imidazole (0.38 mmol, 1.0 eq.) in 2 ml of dry of dimethylformamide was added 15.5 mg of NaH (60%) (0.38 mmol, 1.0 eq.), and the mixture was stirred vigorously for 10 min. before dropwise addition of 0.05 ml of tert-butyl bromoacetate (0.34 mmol, 0.9 eq.). The resulting solution was heated at 70[deg.] C. for 30 min before it was diluted with 20 ml of water, and extracted with 3*30 ml of ethyl acetate. The organic extracts were combined and washed sequentially with water, and brine. The organic phase was dried with MgSO4, filtered, and evaporated to give 60 mg of a slight yellow solid. [0429] To a solution of above solid in 5 ml of CH2Cl2 was added 5 ml of trifluoroacetic acid, and the resulting solution was stirred at room temperature for 3 h. The solvent was then evaporated under vacuum to give 35 mg of final product.

References: [1]Patent: US2003/199458,2003,A1 .Location in patent: Page/Page column 49.

47
[ 17694-68-7 ]
[ 77287-34-4 ]
[ 51746-85-1 ]

References: [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 4968 - 4977.

48
[ 600-00-0 ]
[ 51746-85-1 ]
[ 484673-55-4 ]

Yield	Reaction Conditions	Operation in experiment
33%		To a solution of 3-(LH-IMIDAZOL-4-YL)-PYRIDINE (1 eq) in DMF was added potassium carbonate (2 eq) under dry condition. After stirring for 1 hour, ethyl 2-bromoisobutyrate (5 eq) was added to the mixture. The solution was left stirring over 36 hours at room temperature. The reaction solvent was removed IN VACUO and the solid was diluted with ethyl acetate washed with H2O, NACI (sat. ), dried over sodium sulfate, filtered, and concentrated. The crude product was purified by flash chromatography using a solvent gradient of 97% DCM, 3% MeOH, and 0.1% TEA to yield 2-METHYL-2- (4-PYRIDIN-3-YL-IMIDAZOL-1-YL)-PROPIONIC acid ethyl ester (33%).

References: [1]Patent: WO2004/96822,2004,A2 .Location in patent: Page 247.

49
[ 7252-83-7 ]
[ 51746-85-1 ]
[ 439106-42-0 ]
[ 1207070-57-2 ]

References: [1]Synthetic Communications,2010,vol. 40,p. 81 - 86.

50
[ 51746-85-1 ]
[ 2032-35-1 ]
[ 790300-56-0 ]

References: [1]Synthetic Communications,2010,vol. 40,p. 81 - 86.

51
[ 51746-85-1 ]
[ 2032-35-1 ]
[ 1207070-56-1 ]
[ 794508-41-1 ]

References: [1]Synthetic Communications,2010,vol. 40,p. 81 - 86.

52
N-(2-bromoethyl)phthalimide [ No CAS ]
[ 51746-85-1 ]
[ 1196733-91-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 50℃; for 7h;Cooling with ice;	(1) A solution of <strong>[51746-85-1]3-(1H-imidazol-4-yl)pyridine</strong> (3.0 g) in dimethylformamide (10 ml) and N-(2-bromoethyl)phthalimide (5.26 g) were added to a suspension of sodium hydride (763 mg) in dimethylformamide (10 ml) under ice cooling, and the resulting mixture was stirred at the same temperature for 1 hour, at room temperature for 4 hours, and at 50C for 2 hours. After the reaction mixture was cooled, saturated aqueous sodium hydrogencarbonate, and ethyl acetate were added to the reaction mixture, the layers were separated, and the resulting organic layer was washed with distilled water and saturated brine, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (chloroform:methanol = 9:1) to obtain a phthalimide compound (193.7 mg).

References: [1]Patent: EP2287173,2011,A1 .Location in patent: Page/Page column 57.

53
[ 51746-85-1 ]
[ 1233855-46-3 ]

References: [1]Patent: WO2012/15324,2012,A1 .
[2]Patent: WO2012/15324,2012,A1 .
[3]Patent: WO2014/17938,2014,A2 .

54
[ 51746-85-1 ]
[ 1233855-18-9 ]

References: [1]Patent: WO2012/15324,2012,A1 .
[2]Patent: WO2012/15324,2012,A1 .
[3]Patent: WO2014/17938,2014,A2 .

Historical Records

Technical Information

• Preparation of Amines

Related Parent Nucleus of
[ 51746-85-1 ]

Pyridines

A180241 [39774-25-9]

2-Amino-6-phenylpyridine

Similarity: 0.65

A135446 [823-39-2]

3,4-Dimethylpyridin-2-amine

Similarity: 0.63

A137105 [99132-27-1]

6-Ethyl-N-methylpyridin-2-amine

Similarity: 0.63

A128370 [823-61-0]

3,6-Dimethyl-2-pyridinamine

Similarity: 0.63

A258499 [5407-87-4]

2-Amino-4,6-dimethylpyridine

Similarity: 0.63

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CAS No.: 51746-85-1

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