CAS No. :	22282-75-3
Formula :	C₅H₃FIN
M.W :	222.99
SMILES Code :	IC1=C(F)C=NC=C1
MDL No. :	MFCD03092927
InChI Key :	MSLUTDVOKZOXTA-UHFFFAOYSA-N
Pubchem ID :	10998636

Safety of 3-Fluoro-4-iodopyridine

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H332-H335
Precautionary Statements:	P261-P280-P305+P351+P338

Application In Synthesis of 3-Fluoro-4-iodopyridine

* 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 [ 22282-75-3 ]
Downstream synthetic route of [ 22282-75-3 ]

[ 22282-75-3 ] Synthesis Path-Upstream 1~7

1
[ 372-47-4 ]
[ 22282-75-3 ]

References: [1] Tetrahedron Letters, 2004, vol. 45, # 36, p. 6697 - 6701.
[2] Tetrahedron Letters, 1980, vol. 21, # 43, p. 4137 - 4140.
[3] Heterocycles, 1993, vol. 35, # 1, p. 151 - 169.
[4] Tetrahedron, 1993, vol. 49, # 1, p. 49 - 64.
[5] Heterocycles, 1996, vol. 43, # 8, p. 1641 - 1652.
[6] Patent: US6440972, 2002, B1, .

2
[ 372-47-4 ]
[ 22282-75-3 ]

References: [1] Tetrahedron, 2016, vol. 72, # 17, p. 2196 - 2205.

3
[ 372-47-4 ]
[ 22282-75-3 ]
[ 146141-04-0 ]

References: [1] Tetrahedron, 2016, vol. 72, # 17, p. 2196 - 2205.

4
[ 372-47-4 ]
[ 22282-75-3 ]
[ 146141-04-0 ]

References: [1] Tetrahedron, 2016, vol. 72, # 17, p. 2196 - 2205.

5
[ 22282-75-3 ]
[ 146141-04-0 ]

References: [1] Journal of Organic Chemistry, 1993, vol. 58, # 27, p. 7832 - 7838.
[2] Tetrahedron, 1993, vol. 49, # 1, p. 49 - 64.

6
[ 372-47-4 ]
[ 22282-75-3 ]
[ 146141-04-0 ]

References: [1] Tetrahedron, 2016, vol. 72, # 17, p. 2196 - 2205.

7
[ 372-47-4 ]
[ 22282-75-3 ]
[ 146141-04-0 ]

References: [1] Tetrahedron, 2016, vol. 72, # 17, p. 2196 - 2205.

[ 22282-75-3 ] Synthesis Path-Downstream 1~54

1
[ 372-47-4 ]
[ 22282-75-3 ]

Yield	Reaction Conditions	Operation in experiment
	With iodine; lithium diisopropyl amide; In tetrahydrofuran; diethyl ether; n-heptane; water;	The starting material was prepared as follows: A solution of 3-fluoropyridine (19.4 g) in dry tetrahydrofuran (20 ml) was added dropwise over 30 minutes, under an atmosphere of argon, to a stirred solution of 2M lithium diisopropylamide/tetrahydrofutran/heptane (100 ml) in dry tetrahydrofuran (700 ml) at -70° C. The mixture was stirred at -70° C. for 4 hours. A solution of iodine (50.7 g) in dry tetrahydrofuran (160 ml) was added dropwise to this stirred suspension at -70° C. over 45 minutes and stirring was continued for a further 45 minutes. A mixture of tetrahydrofuran (160 ml)/water (40 ml) was added to the resulting solution at -70° C. The solution was allowed to warm to 0° C. Water (200 ml) was added and diethyl ether (400 ml). The mixture was allowed to stand at ambient temperature for 16 hours. The ether layer was separated. The aqueous layer was extracted with ether (2100 ml). The ether layers were all combined, washed with aqueous sodium thiosulphate solution (2250 ml) and saturated brine (2*100 ml), dried (Na2O4) and evaporated to low bulk. The residue was dissolved in dry diethyl ether and the solution was cooled to -50° C. The solid, which had separated, was filtered off and washed with pentane at -50° C. to give 3-fluoro-4-iodopyridine (22.8 g) as a white solid: NMR (CDCl3): 7.75 (t, 1H), 8.05 (d, 1H), 8.3 5 (s, 1H); m/z 223 M.

References: [1]Tetrahedron Letters,2004,vol. 45,p. 6697 - 6701.
[2]Tetrahedron Letters,1980,vol. 21,p. 4137 - 4140.
[3]Heterocycles,1993,vol. 35,p. 151 - 169.
[4]Tetrahedron,1993,vol. 49,p. 49 - 64.
[5]Heterocycles,1996,vol. 43,p. 1641 - 1652.
[6]Patent: US6440972,2002,B1 .

2
[ 124-38-9 ]
[ 22282-75-3 ]
3-Fluoro-2-iodo-4-pyridinecarboxylic acid [ No CAS ]

References: [1]Journal of Organic Chemistry,1993,vol. 58,p. 7832 - 7838.

3
[ 22282-75-3 ]
[ 146140-95-6 ]
[ 146141-07-3 ]

References: [1]Tetrahedron,1993,vol. 49,p. 49 - 64.
[2]Tetrahedron Letters,1993,vol. 34,p. 7917 - 7918.

4
[ 22282-75-3 ]
5-methoxy-2-(pivaloylamino)phenylboronic acid [ No CAS ]
[ 155727-47-2 ]

References: [1]Tetrahedron Letters,1994,vol. 35,p. 2003 - 2004.
[2]Journal of Heterocyclic Chemistry,1995,vol. 32,p. 1171 - 1175.

5
[ 22282-75-3 ]
[ 146141-04-0 ]

References: [1]Journal of Organic Chemistry,1993,vol. 58,p. 7832 - 7838.
[2]Tetrahedron,1993,vol. 49,p. 49 - 64.

6
[ 22282-75-3 ]
4-Deuterio-3-fluoro-2-iodopyridine [ No CAS ]

References: [1]Journal of Organic Chemistry,1993,vol. 58,p. 7832 - 7838.

7
[ 22282-75-3 ]
3-Fluoro-2,4-diiodopyridine [ No CAS ]

References: [1]Journal of Organic Chemistry,1993,vol. 58,p. 7832 - 7838.

8
[ 22282-75-3 ]
[ 100-52-7 ]
(3-Fluoro-2-iodo-4-pyridylphenyl)methanol [ No CAS ]

References: [1]Journal of Organic Chemistry,1993,vol. 58,p. 7832 - 7838.

9
[ 22282-75-3 ]
[ 120-14-9 ]
1-(3-Fluoro-2-iodo-4-pyridyl)-1-(3,4-dimethoxyphenyl)methanol [ No CAS ]

References: [1]Journal of Organic Chemistry,1993,vol. 58,p. 7832 - 7838.

10
[ 22282-75-3 ]
[ 74-88-4 ]
[ 153035-05-3 ]

References: [1]Journal of Organic Chemistry,1993,vol. 58,p. 7832 - 7838.

11
[ 22282-75-3 ]
6-methoxy-2-(pivaloylamino)phenylboronic acid [ No CAS ]
2,2-dimethyl-N-(3-methoxy-2-(3-fluoro-4-pyridyl)phenyl)propanamide [ No CAS ]

References: [1]Journal of Heterocyclic Chemistry,1995,vol. 32,p. 1171 - 1175.

12
[ 22282-75-3 ]
3-methoxy-2-(pivaloylamino)phenylboronic acid [ No CAS ]
[ 170959-26-9 ]

References: [1]Journal of Heterocyclic Chemistry,1995,vol. 32,p. 1171 - 1175.

13
[ 22282-75-3 ]
3,4-dichloro-2-(pivaloylamino)benzeneboronic acid [ No CAS ]
7,8-dichloro-β-carboline [ No CAS ]

References: [1]Synthetic Communications,1995,vol. 25,p. 2901 - 2908.

14
[ 22282-75-3 ]
3,4-dichloro-2-(pivaloylamino)benzeneboronic acid [ No CAS ]
2,3-Dichloro-6-(3-fluoro-pyridin-4-yl)-phenylamine [ No CAS ]
N-[2,3-Dichloro-6-(3-fluoro-pyridin-4-yl)-phenyl]-2,2-dimethyl-propionamide [ No CAS ]

References: [1]Synthetic Communications,1995,vol. 25,p. 2901 - 2908.

15
[ 22282-75-3 ]
3-carboxy-4-methoxy-2-(pivaloylamino)phenylboronic acid [ No CAS ]
6-methoxy-2-pivaloylamino-3-(3-fluoro-4-pyridyl)phenylcarboxylic acid [ No CAS ]

References: [1]Journal of Heterocyclic Chemistry,1995,vol. 32,p. 1171 - 1175.

16
N-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-methane-sulfonamide [ No CAS ]
[ 22282-75-3 ]
9-Methylsulfonyl-β-carboline [ No CAS ]

References: [1]Organic Letters,2007,vol. 9,p. 4893 - 4896.

17
[ 22282-75-3 ]
[ 106531-57-1 ]

References: [1]Heterocycles,1996,vol. 43,p. 1641 - 1652.

18
[ 22282-75-3 ]
3,3-Dimethyl-2,3-dihydro-furo[2,3-c]pyridine [ No CAS ]

References: [1]Heterocycles,1996,vol. 43,p. 1641 - 1652.

19
[ 22282-75-3 ]
3-Ethyl-furo[2,3-c]pyridine [ No CAS ]

References: [1]Heterocycles,1996,vol. 43,p. 1641 - 1652.

20
[ 22282-75-3 ]
bauerine B [ No CAS ]

References: [1]Synthetic Communications,1995,vol. 25,p. 2901 - 2908.

21
[ 22282-75-3 ]
[ 99896-91-0 ]

References: [1]Journal of Heterocyclic Chemistry,1995,vol. 32,p. 1171 - 1175.

22
[ 22282-75-3 ]
[ 58982-28-8 ]

References: [1]Journal of Heterocyclic Chemistry,1995,vol. 32,p. 1171 - 1175.
[2]Tetrahedron Letters,1994,vol. 35,p. 2003 - 2004.

23
[ 22282-75-3 ]
8-hydroxy-β-carboline [ No CAS ]

References: [1]Journal of Heterocyclic Chemistry,1995,vol. 32,p. 1171 - 1175.

24
[ 22282-75-3 ]
5-hydroxy-β-carboline [ No CAS ]

References: [1]Journal of Heterocyclic Chemistry,1995,vol. 32,p. 1171 - 1175.

25
[ 22282-75-3 ]
8-hydroxy-1-vinyl-β-carboline [ No CAS ]

References: [1]Journal of Heterocyclic Chemistry,1995,vol. 32,p. 1171 - 1175.

26
[ 22282-75-3 ]
[ 170959-20-3 ]

References: [1]Journal of Heterocyclic Chemistry,1995,vol. 32,p. 1171 - 1175.

27
[ 22282-75-3 ]
[ 170959-19-0 ]

References: [1]Journal of Heterocyclic Chemistry,1995,vol. 32,p. 1171 - 1175.

28
[ 22282-75-3 ]
[ 67767-19-5 ]

References: [1]Tetrahedron Letters,1994,vol. 35,p. 2003 - 2004.

29
[ 22282-75-3 ]
[ 155727-48-3 ]

References: [1]Tetrahedron Letters,1994,vol. 35,p. 2003 - 2004.

30
[ 22282-75-3 ]
[ 245-08-9 ]

References: [1]Journal of Organic Chemistry,1993,vol. 58,p. 7832 - 7838.
[2]Tetrahedron,1993,vol. 49,p. 49 - 64.

31
[ 22282-75-3 ]
[ 146141-10-8 ]

References: [1]Journal of Organic Chemistry,1993,vol. 58,p. 7832 - 7838.
[2]Tetrahedron,1993,vol. 49,p. 49 - 64.

32
[ 22282-75-3 ]
[ 155246-38-1 ]

References: [1]Tetrahedron Letters,1993,vol. 34,p. 7917 - 7918.

33
[ 22282-75-3 ]
[ 155246-39-2 ]

References: [1]Tetrahedron Letters,1993,vol. 34,p. 7917 - 7918.

34
[ 22282-75-3 ]
[ 157023-34-2 ]
4-[(3-fluoro-pyridin-4-ylamino)-methyl]-piperidine-1-carboxylic acid benzyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 56 4-[(3-Fluoro-pyridin-4-ylamino)-methyl]-piperidine-1-carboxylic acid benzyl ester TFA salt A mixture of benzyl-4-(aminomethyl)piperidine-1-carboxylate (EXAMPLE 13, Step 1, 0.20 g, 0.81 mmol), <strong>[22282-75-3]3-fluoro-4-iodo-pyridine</strong> (Tetrahedron, 49:49-64(1993) (0.18 g, 0.81 mmol) in IPA (0.1 mL) was heated at 100 C. in a sealed reaction tube for 100 h, then concentrated in vacuo. The residue was purified by reversed phase chromatography to give 4-[(3-fluoro-pyridin-4-ylamino)-methyl]-piperidine-1-carboxylic acid benzyl ester as a TFA salt. M.S.(M+1):344.36.

References: [1]Patent: US2002/165241,2002,A1 .

35
[ 52409-22-0 ]
[ 22282-75-3 ]
[ 6163-58-2 ]
[ 203520-03-0 ]
[ 211820-04-1 ]

Yield	Reaction Conditions	Operation in experiment
	In 1,4-dioxane; dichloromethane;	To a suspension of <strong>[22282-75-3]3-fluoro-4-iodopyridine</strong> (2.23 g), 1-(tert-butoxycarbonyl)-4-(piperidin-4-ylcarbonyl)piperazine (1.49 g) and sodium t-butoxide (1.06 g) in 1,4-dioxan (20 ml) was added tris(dibenzylidene acetone)dipalladium(0) (0.09 g) and tri-o-tolylphosphine (0.12 g) and the mixture heated at reflux for 3 hours. The mixture was diluted with diethyl ether and washed with saturated aqueous sodium chloride solution, dried (Na2SO4) and evaporated. The residue was purified by chromatography on alumina (N32-63) eluding with 0.4percent methanol in dichloromethane to give as a solid, 1-(tert-butoxycarbonyl)-4-[1-(3-fluoro-4-pyridyl)piperidin-4-ylcarbonyl]piperazine (0.70 g). 1H-NMR (CDCl3): 1.45 (s, 9H), 1.80 (m, 2H), 2.00 (m, 2H), 2.65 (m, 1H), 2.90 (m, 2H), 3.40 (m, 8H), 3.80 (m, 2H), 6.70 (dd, 1H), 8.10 (d, 1H) and 8.20 (d, 1H); m/z 393 (M+1).
	In 1,4-dioxane; dichloromethane;	To a suspension of <strong>[22282-75-3]3-fluoro-4-iodopyridine</strong> (2.23 g), 1-(tert-butoxycarbonyl)-4-(piperidin-4-ylcarbonyl) piperazine (1.49 g) and sodium t-butoxide (1.06 g) in 1,4-dioxan (20 ml) was added tris(dibenzylidene acetone)dipalladium(0) (0.09 g) and tri-o-tolylphosphine (0.12 g) and the mixture heated at reflux for 3 hours. The mixture was diluted with diethyl ether and washed with saturated aqueous sodium chloride solution. dried (Na2SO4) and evaporated. The residue was purified by chromatography on alumina (N32-63) eluding with 0.4percent methanol in dichloromethane to give as a solid, 1-(tert-butoxycarbonyl)-4-[1-(3-fluoro-4-pyridyl)piperidin-4-ylcarbonyl]piperazine (0.70 g). 1H-NMR (CDCl3): 1.45 (s, 9H), 1.80 (m, 2H), 2.00 (m, 2H), 2.65 (m, 1H), 2.90 (m, 2H), 3.40 (m, 8H), 3.80 (m, 2H), 6.70 (dd, 1H), 8.10 (d, 1H) and 8.20 (d, 1H); m/z 393 (M+1).

References: [1]Patent: US6440972,2002,B1 .
[2]Patent: US6440972,2002,B1 .

36
[ 203520-35-8 ]
[ 22282-75-3 ]
[ 6163-58-2 ]
[ 211820-06-3 ]

Yield	Reaction Conditions	Operation in experiment
	tris-(dibenzylideneacetone)dipalladium(0); In 1,4-dioxane; methanol; dichloromethane;	Tris(dibenzylideneacetone)dipalladium(0) (0.184 g) and tri-o-tolylphosphine (0.244 g) were added to a suspension of <strong>[22282-75-3]3-fluoro-4-iodopyridine</strong> (4.46 g), 1-[1-(t-butoxycarbonyl)piperazin-4-ylcarbonyl]piperazine (3.0 g) and sodium t-butoxide (2.12 g) in dry 1,4-dioxane (40 ml) under an atmosphere of argon. The mixture was heated at 100° C. for 18 hours. The mixture was cooled, diluted with diethyl ether (200 ml) and washed with saturated brine (40 ml). The aqueous layer was back-extracted with diethyl ether (2100 ml). The ether layers were all combined, washed with saturated brine (2100 ml), dried (Na2SO4) and evaporated. The residual oil was purified by chromatography on alumina (N32-63) using 0.1-0.4percent methanol in dichloromethane as eluent to give 1-(t-butoxycarbonyl)-4-[1-(3-fluoro-4-pyridyl)piperazin-4-ylcarbonyl]piperazine (1.7 g) as an orange solid: NMR (CDCl3): 1.47 (s, 9H), 3.25 (m, 8H), 3.45 (m, 8H), 6.75 (dd, 1H), 8.20 (dd, 2H); m/z 394 (M+1).

References: [1]Patent: US6440972,2002,B1 .

37
[ 22282-75-3 ]
[ 95-92-1 ]
[ 388612-88-2 ]

Yield	Reaction Conditions	Operation in experiment
		1 Ethyl (3-fluoro-2-iodopyridin-4-yl)oxoacetate n-Butyllithium (1.59M in hexane) (1.75 ml, 2.78 mmol) was added to a solution of diisopropylamine (390 mul, 2.78 mmol) in tetrahydrofuran (10 ml) at -78 C., and the mixture was warmed up to 0 C., then stirred for 30 minutes. The mixture was again cooled down to -78 C. A solution of <strong>[22282-75-3]3-fluoro-4-iodopyridine</strong> (500 mg, 2.24 mmol) synthesised by the method of P. Rocca et. al. (Tetrahedron 49,49-64(1993)) in tetrahydrofuran (4 ml) was added to said mixture, and the resulting mixture was stirred for 1.5 hours. The reaction mixture was dropwise added to a solution of diethyl oxalate (900 mul, 6.63 mmol) in tetrahydrofuran (10 ml) at -78 C. under stirring. The mixture was warmed up to room temperature and stirred for 20 minutes. Aqueous ammonium chloride was added to the reaction mixture, and the mixture was extracted with chloroform. The extract was dried over anhydrous magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane:ethyl acetate, 3:2) to give the title compound (659 mg).

References: [1]Patent: US2003/203907,2003,A1 .Location in patent: Page/Page column 54.

38
[ 807618-13-9 ]
[ 22282-75-3 ]
[ 1104082-65-6 ]

Yield	Reaction Conditions	Operation in experiment
	(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; copper(l) iodide; In ISOPROPYLAMIDE; at 80℃;	Synthesis of Example 10: Intermediate 10a): [Show Image] A flame dried Schlenk flask was charged with <strong>[22282-75-3]3-fluoro-4-iodopyridine</strong> (1.00 g), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (110 mg), copper(I) iodide (51 mg), and dry N,N-dimethylacetamide (6 ml). The resulting mixture was degassed with alternating vacuum/argon purges. Then 1-tert-butoxycarbonylpiperidin-4-yl)(iodo)zinc (6.28 mmol, prepared as described above) was added. The mixture was degassed once again and then heated to 80 °C overnight. The mainpart of N,N-dimethylacetamide was then evaporated and the remainder was taken up in a mixture of EtOAc and water (each with 100 ml). The mixture was then filtered through Celite and transferred into a separatory funnel. The phases were separated and the water layer was extracted with EtOAc (3 x 30 ml). The combined organic layer was washed with water and brine (each with 75 ml), dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by column chromatography to furnish the desired compound in form of a brownish solid.

References: [1]Patent: EP2019100,2009,A1 .Location in patent: Page/Page column 37.

39
[ 10075-50-0 ]
[ 22282-75-3 ]
[ 1255145-25-5 ]

Yield	Reaction Conditions	Operation in experiment
46%	With copper(l) iodide; potassium carbonate; lithium chloride; In N,N-dimethyl-formamide; at 120℃; for 64h;Inert atmosphere;	Description 205-bromo-1-(3-fluoro-pyridin-4-yl)-1H-indole (D20)5-bromo-1H-indole [CA.S. 10075-50-0] (2 g, 10.202 mmol) was dissolved in DMF (16 ml). A nitrogen stream was bubbled through the mixture and then were added 3-Fluoro- 4-iodopyridine [CA.S. 22282-75-3] (2.502 g, 11.222 mmol), lithium chloride (0.432 g, 10.202 mmol), copper(I) iodide (0.0195 g, 0.102 mmol) and K2CO3 (4.23 g, 30.605 mmol). The reaction mixture was heated at 120 0C for 2 days. After cooling to room temperature, the reaction mixture was refilled with lithium chloride (0.100 g) and (copper(I) iodide (0.010) stirred at 1200C for 16 h. After cooling to room temperature, the reaction mixture was washed with NH3 (aqueous sat. solution) and extracted with DCM. The organic layer was separated, washed with water, dried (Na2SO4), and the solvent was evaporated in vacuo. The residue was purified by column chromatography (silica gel; eluent: Heptane/EtOAc up to 15percent as eluent). The desired fractions were collected and the solvent was evaporated in vacuo to yield intermediate compound D20 (1.37 g, 46 percent).

References: [1]Patent: WO2010/130422,2010,A1 .Location in patent: Page/Page column 60.

40
C₁₁H₁₁FN₂ [ No CAS ]
[ 22282-75-3 ]
3-fluoro-4-(3-fluoro-3-(pyridin-2-ylethynyl)pyrrolidin-1-yl)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27.2%	With caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; bis(dibenzylideneacetone)-palladium(0); In N,N-dimethyl-formamide; at 120℃; for 1h;Inert atmosphere;	To a solution of 1 (15mg, 0.079mmol), 2 (35mg, 0.158mmol) and Cs2CO3 (128mg, 0.395mmol) in DMF (lmL) were added 2 mg of Pd(dba)2 and 2 mg of Xantphos. The suspension was degassed under vacuum and purged with N2 several times. The mixture was stirred at 120 °C for 1h. LCMS showed the SM was consumed completely. Then the reaction mixture was diluted with EA (10mL) and washed with brine (2mL) twice. The organic solution was dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure and purified by p-TLC to give the desired compound Compound 217 (6mg, yield: 27.2percent). LCMS: m/z, 286.1 (M+H)+; 1HNMR (CDCl3, 400MHz): delta 8.62(d, J=4.8, 1H), 8.17(d, J=5.6, 1H), 8.08(d, J=5.2, 1H), 7.69~7.74(m, 1H), 7.52(d, J=8.0, 1H), 7.31~7.33(m, 1H), 6.47(dd, J1=5.6,J2=8.0, 1H), 4.03~4.15(m, 2H), 3.71~3.78(m, 2H), 2.58~2.74(m, 1H), 2.40~2.46(m, 1H).

References: [1]Patent: WO2014/124560,2014,A1 .Location in patent: Page/Page column 94; 95.

41
[ 1160004-88-5 ]
[ 22282-75-3 ]
(3S,4S)-tert-butyl 3-azido-4-((3-(3-fluoropyridin-4-yl)prop-2-yn-1-yl)oxy)pyrrolidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
15%		A mixture of Cul (20 mg, 0.10 mmol), Pd(PPh3)4(24 mg, 0.021 mmol) and 3-fluoro- 4-iodopyridine (469 mg, 2.10 mmol) in Et3N (28 ml) under nitrogen was stirred at r.t. for 60 min. Then, a solution of (3S,4S)-tert-butyl-3-azido-4-(prop-2- ynyloxy)pyrrolidine-1 -carboxylate (560 mg, 2.10 mmol) in Et3N (17 ml) was added and the mixture was heated at 60 °C overnight. After cooling to r.t., water was added and the mixture was extracted with EtOAc. The organic phase was washed with brine, dried over Na2S04, filtered and concentrated. Purification by flash chromatography, silica gel, gradient hexane to ethyl acetate, afforded the desired product (398 mg, 52percent) and the corresponding cyclic intermediate of general formula (V) (1 18 mg, 15percent yield).1H-NMR (400MHz, CDCI3): mixture of two rotamers, delta ppm: 8.50 (s, 1 H), 8.39 (d, J = 5 Hz, 1 H), 7.33 (t, J = 5 Hz, 1 H), 4.50 (m, 2H), 4.15 (m, 1 H), 4.10 (m, 1 H), 3.65 (m, 2H), 3.47 (m, 2H), 1.46 (s, 9H).

References: [1]Patent: WO2014/170494,2014,A1 .Location in patent: Page/Page column 34; 35.

42
[ 1160004-88-5 ]
[ 22282-75-3 ]
(3S,4S)-tert-butyl 3-azido-4-((3-(3-fluoropyridin-4-yl)prop-2-yn-1-yl)oxy)pyrrolidine-1-carboxylate [ No CAS ]
C₁₇H₂₀FN₅O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
15%; 15%		b) Synthesis of (3S,4S)-tert-butyl-3-azido-4-((3-(3-fluoropyridin-4-yl)prop-2-yn-1-yl)oxy)pyrrolidine-1-carboxylate A mixture of Cul (20 mg, 0.10 mmol), Pd(PPh3)4 (24 mg, 0.021 mmol) and <strong>[22282-75-3]3-fluoro-4-iodopyridine</strong> (469 mg, 2.10 mmol) in Et3N (28 ml) under nitrogen was stirred at r.t. for 60 min. Then, a solution of (3S,4S)-tert-butyl-3-azido-4-(prop-2-ynyloxy)pyrrolidine-1-carboxylate (560 mg, 2.10 mmol) in Et3N (17 ml) was added and the mixture was heated at 60 ºC overnight. After cooling to r.t., water was added and the mixture was extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated. Purification by flash chromatography, silica gel, gradient hexane to ethyl acetate, afforded the desired product (398 mg, 52percent) and the corresponding cyclic intermediate of general formula (V) (118 mg, 15percent yield). 1H-NMR (400MHz, CDCl3): mixture of two rotamers, delta ppm: 8.50 (s, 1 H), 8.39 (d, J = 5 Hz, 1 H), 7.33 (t, J = 5 Hz, 1 H), 4.50 (m, 2H), 4.15 (m, 1 H), 4.10 (m, 1 H), 3.65 (m, 2H), 3.47 (m, 2H), 1.46 (s, 9H).

References: [1]Patent: EP2792679,2014,A1 .Location in patent: Page/Page column 0092-0093.

43
[ 22282-75-3 ]
[ 1692-15-5 ]
[ 1131-30-2 ]

References: [1]Journal of the American Chemical Society,2015,vol. 137,p. 2852 - 2855.

44
[ 22282-75-3 ]
[ 1692-15-5 ]
3-fluoro-1,1'-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H,1'H-4,4'-bipyridinylidene [ No CAS ]

References: [1]Journal of the American Chemical Society,2015,vol. 137,p. 2852 - 2855.

45
3-amino-5-chloropyrazine-2-thiol [ No CAS ]
[ 22282-75-3 ]
6-chloro-3-((3-fluoropyridin-4-yl)thio)pyrazin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25 mg	With tris-(dibenzylideneacetone)dipalladium(0); N-ethyl-N,N-diisopropylamine; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 105℃; for 10h;	00287] A mixture of 3-amino-5-chloropyrazine-2-thiol (50 mg, 0.181 mmol), 3-fluoro- 4-iodopyridine (121 mg, 0.544 mmol), Xantphos (10.5 mg, 0.018 mmol), Pd2(dba)3 (8.3 mg, 0.009 mmol), and DIPEA (95 muEpsilon, 0.544 mmol) in dioxane (degassed, 1.8 mL) was stirred for 10 h at 105 °C. After cooling to RT, the reaction was filtered through a pad of Celite followed by EtO Ac (25 mL) wash. The combined filtrates were concentrated under reduced pressure and the resulting residue was purified by silica chromatography (0 to 40percent gradient of EtO Ac/heptane (containing 2percent of Et3N)) to give 6-chloro-3-((3-fluoropyridin-4-yl)thio)pyrazin-2-amine (25 mg, 0.097 mmol). MS m/z 257.0 (M+H)+.

References: [1]Patent: WO2015/107494,2015,A1 .Location in patent: Paragraph 00287.

46
[ 372-47-4 ]
[ 22282-75-3 ]
[ 146141-04-0 ]
3-Fluoro-2,4-diiodopyridine [ No CAS ]

References: [1]Tetrahedron,2016,vol. 72,p. 2196 - 2205.

47
[ 372-47-4 ]
[ 22282-75-3 ]
3-Fluoro-2,4-diiodopyridine [ No CAS ]

References: [1]Tetrahedron,2016,vol. 72,p. 2196 - 2205.

48
[ 372-47-4 ]
[ 22282-75-3 ]
[ 146141-04-0 ]

References: [1]Tetrahedron,2016,vol. 72,p. 2196 - 2205.

49
3-amino-5-chloropyrazine-2-thiol trifluoroacetate [ No CAS ]
[ 22282-75-3 ]
6-chloro-3-((3-fluoropyridin-4-yl)thio)pyrazin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25 mg	With tris-(dibenzylideneacetone)dipalladium(0); N-ethyl-N,N-diisopropylamine; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 105℃; for 10h;	A mixture of 3-amino-5-chloropyrazine-2-thiol (50mg, 0.181 mmol), <strong>[22282-75-3]3-fluoro-4-iodopyridine</strong> (121 mg, 0.544 mmol), Xantphos (10.5 mg, 0.018 mmol), Pd2(dba)3 (8.3 mg, 0.009 mmol), and DIPEA (95 IL, 0.544 mmol) in dioxane (degassed, 1.8 mE) was stirred for 10 hat 105° C. Afier cooling to RT, the reaction was filtered through a pad of Celite followed by EtOAc (25 mE) wash. The combined filtrates were concentrated under reduced pressure and the resulting residue was purified by silica chromatography (0 to 40percent gradient of EtOAc/heptane (containing 2percent of Et3N)) to give 6-chloro-3-((3-fluoropyridin-4-yl)thio)pyrazin-2- amine (25 mg, 0.097 mmol). MS mlz 257.0 (M+H).

References: [1]Patent: US2017/1975,2017,A1 .Location in patent: Paragraph 0320; 0321.

50
[ 64185-12-2 ]
[ 22282-75-3 ]
3-fluoro-4-(3,3,3-trifluoroprop-1-yn-1-yl)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31%	With tetrakis(triphenylphosphine) palladium(0); sodium; In toluene; at 130℃; for 5h;	Preparation 1A 3-fluoro-4-(3,3,3-trifluoroprop-1-yn-1-yl)pyridine A mixture of <strong>[22282-75-3]3-fluoro-4-iodopyridine</strong> (1 g, 4.48 mmol), 1-tributylstannyl-3,3,3-trifluoro-1-propyne (2.3 g, 5.38 mmol, 90percent) and Pd(PPh3)4 (259 mg, 0.045 mmol) in toluene (15 mL) was heated for 5 hr at 130° C. under Na in a microwave oven. The mixture was concentrated and purified by flash column chromatography on silica gel (EtOAc/Hex=0percent-20percent) to afford the title compound (260 mg, 31percent). [M+H] calculated for C8H3F4N: 190; found: 190.

References: [1]Patent: US2017/298044,2017,A1 .Location in patent: Paragraph 0146; 0147; 0175; 0176.

51
[ 22282-75-3 ]
3-fluoro-4-{1-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)-1H-1,2,3-triazol-4-yl}pyridine [ No CAS ]
3-fluoro-4-{1-[(4-methoxyphenyl)methyl]-4-(trifluoromethyl)-1H-1,2,3-triazol-5-yl}pyridine [ No CAS ]

References: [1]Patent: US2017/298044,2017,A1 .

52
[ 22282-75-3 ]
3-fluoro-4-[5-(trifluoromethyl)-1H-1,2,3-triazol-4-yl]pyridine [ No CAS ]

References: [1]Patent: US2017/298044,2017,A1 .

53
[ 22282-75-3 ]
N-(5-chloro-2-fluorophenyl)-4-[5-(trifluoromethyl)-1H-1,2,3-triazol-4-yl]pyridin-3-amine [ No CAS ]

References: [1]Patent: US2017/298044,2017,A1 .

54
N-(1-methylpiperidin-4-yl)-N-(1H-pyrazol-3-yl)thiophene-2-carboxamide [ No CAS ]
[ 22282-75-3 ]
N-[1-(3-fluoropyridin-4-yl)-1H-pyrazol-3-yl]-N-(1-methylpiperidin-4-yl)thiophene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With copper(l) iodide; trans-1,2-Diaminocyclohexane; caesium carbonate; In acetonitrile; for 6h;Reflux;	General procedure: Arylation conditions A: N,N,N',N'-Tetramethylethane-1,2-diamine (21 muL, 0.14 mmol) was added to a suspension of N-(1-methylpiperidin-4-yl)-N-(1H-pyrazol-3- yl)thiophene-2-carboxamide (Intermediate C1, 100 mg, 0.34 mmol), 2-iodopyridine (44 muL, 0.41 mmol) and Cs2CO3 (235 mg, 0.72 mmol) in MeCN (8 mL). The reaction mixture was deoxygenated, CuI (13 mg, 0.07 mmol) was added and it was heated under reflux for 6 h. It was cooled down to room temperature, poured into NaHCO3 (saturated aqueous solution, 10 mL) and extracted with CH2Cl2. The combined organic layers were dried over Na2SO4 (anhydrous), filtered and concentrated. The crude residue was purified by flash chromatography on SiO2 (CH2Cl2/MeOH/NH4OH 97:3:1), to afford 118 mg of title compound (beige solid, 93percent yield). HPLC-MS (Method G): Ret, 14.94 min; ESI+-MS m/z, 368 (M+1). Arylation conditions B: (±)-trans-1,2-diaminocyclohexane was used instead of N,N,N',N'-tetramethylethane-1,2-diamine

References: [1]Patent: WO2017/178510,2017,A1 .Location in patent: Page/Page column 265; 266.

Historical Records

Technical Information

• Alkyl Halide Occurrence • General Reactivity • Hiyama Cross-Coupling Reaction • Kinetics of Alkyl Halides • Preparation of Amines • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Dihalides • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling

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CAS No.: 22282-75-3

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CAS No.: 22282-75-3

Alternative Products

Product Details of 3-Fluoro-4-iodopyridine

Safety of 3-Fluoro-4-iodopyridine

Application In Synthesis of 3-Fluoro-4-iodopyridine

[ 22282-75-3 ] Synthesis Path-Upstream 1~7

[ 22282-75-3 ] Synthesis Path-Downstream 1~54

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