2343-22-8|5-Fluoroindoline| Ambeed

CAS No. :	2343-22-8
Formula :	C₈H₈FN
M.W :	137.15
SMILES Code :	FC1=CC2=C(NCC2)C=C1
MDL No. :	MFCD00214461
InChI Key :	NXQRMQIYCWFDGP-UHFFFAOYSA-N
Pubchem ID :	2774463

Safety of [ 2343-22-8 ]

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

Application In Synthesis of [ 2343-22-8 ]

* 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.

Downstream synthetic route of [ 2343-22-8 ]

[ 2343-22-8 ] Synthesis Path-Downstream 1~55

1
[ 2343-22-8 ]
C₃₆H₄₂N₂O₇ [ No CAS ]
[ 1025818-11-4 ]

References: [1]Journal of Medicinal Chemistry,1998,vol. 41,p. 2806 - 2818.

2
[ 2343-22-8 ]
[ 200940-27-8 ]
5-fluoro-2,3-dihydro-indole-1-carboxylic acid [6-(2-methyl-pyridin-3-yloxy)-pyridin-3-yl]-amide [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2000,vol. 10,p. 1863 - 1866.

3
[ 56341-41-4 ]
[ 2343-22-8 ]

References: [1]Journal of Fluorine Chemistry,2001,vol. 111,p. 1 - 10.
[2]Journal of Fluorine Chemistry,2001,vol. 111,p. 1 - 10.

4
[ 399-52-0 ]
[ 2343-22-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium cyanoborohydride; at 20℃; for 20h;	Dissolve 5-fluoroindole (1.0 g) in CH3COOH (10 0 mL) under nitrogen atmosphere. Add anhydrous powdered NaCNBH3 (1.44 g) to this mixture and stir at room temperature for 20 hours. Concentrate the reaction mixture under vacuum, dilute with water (50 mL), adjust the pH of the reaction mixture to 9.0, extract with CH2Cl2 (2 x 75 mL) and dry over MgSO4. Filter and concentrate under vacuum to afford crude product. Puϖfy the crude by flash column chromatography using 25% EtOAc / hexane to afford the title product.
	With sodium cyanoborohydride; acetic acid; at 20℃; for 1h;	5-Fluoroindole (3 g, 22.2 mmol) in glacial acetic acid (35 mL) was treated with sodium cyanoborohydride (2.79 mg, 44.4 mmol) portionwise at room temperature with stirring. After one hour, the reaction was diluted with water and basified with 40% sodium hydroxide with cooling. The mixture was extracted 3 times with dichloromethane, dried and concentrated to give 5-fluoroindoline. It was used in the next step without further purification. 1H-NMR (300 MHz, dimethylsulfoxide-d6) δ 6.86 (m, 1H), 6.68 (dt, 1H), 6.42 (dd, 1H), 5.32 (br s, 1H, NH), 3.38 (m, 2H, CH2), 2.87 (t, 2H, CH2).
	With sodium cyanoborohydride; In acetic acid; at 20℃; for 1h;	[0280] 5-Fluoroindole (3 g, 22.2 mmol) in glacial acetic acid (35 mL) was treated with sodium cyanoborohydride (2.79 mg, 44.4 mmol) portionwise at room temperature with stirring. After one hour, the reaction was diluted with water and basified with 40% sodium hydroxide with cooling. The mixture was extracted 3 times with dichloromethane, dried and concentrated to give 5-fluoroindoline. It was used in the next step without further purification. 1H-NMR (300 MHz, dimethylsulfoxide-d6) δ 6.86 (m, 1H), 6.68 (dt, 1H), 6.42 (dd, 1H), 5.32 (br s, 1H, NH), 3.38 (m, 2H, CH2), 2.87 (t, 2H, CH2).

	With sodium tetrahydroborate; acetic acid; at 10 - 20℃; for 2h;	5-Fluoro-1H-indole 16a (1000 mg, 7.4 mmol, Shanghai Bied Chemical Reagent Co., Ltd.) was dissolved in acetic acid(12 mL), cooled to 10 to 15 C, sodium borohydride (930 mg, 14.8 mmol) was added in portions, and the mixture was slowly warmed to room temperature for 2 hours.The reaction solution was distilled under reduced pressure to remove an organic solvent. The crude title compound 16b (2000 mg) was obtained.
	With sodium cyanoborohydride; acetic acid; at 20℃;	General procedure: To a solution ofcompound 7 (1 mmol) in glacial acetic acid (10 mL) at room temperature, sodium cyanoborohydride (0.19 g, 3 mmol) was added.Then, the reaction was stirred at room temperature, monitored byTLC. Basification of the solution by NaHCO3 (satd) was accomplished until pH value was about 8. The solutionwas extracted with CH2Cl2. The combined organic layers were dried by MgSO4 and concentrated in vacuo to afford compound 8 for the next step without further purification.
	With hydrogen; In isopropyl alcohol; at 100℃; for 12h;Autoclave;	General procedure: Hydrogenation was carried out in a stainless-steel autoclave equipped with a pressurecontrol system. Typically, 1 mmol of quinolines and 10 mg of various catalysts weremixed in 2 mL of isopropanol. The reactions were performed in an autoclave purgedwith 1 MPa of H2 at 80 oC. The products were analyzed by gas chromatography-massspectrometer (GC-MS) and GC with m-xylene as the internal standard.

References: [1]Organic Letters,2011,vol. 13,p. 5124 - 5127.
[2]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 6073 - 6084.
[3]Organic Letters,2020.
[4]Organic Letters,2020,vol. 22,p. 4222 - 4227.
[5]Chemical Communications,2017,vol. 53,p. 9262 - 9264.
[6]Tetrahedron Letters,2005,vol. 46,p. 1423 - 1425.
[7]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3287 - 3291.
[8]Patent: WO2006/65872,2006,A1 .Location in patent: Page/Page column 49.
[9]Patent: US2004/204407,2004,A1 .Location in patent: Page/Page column 27.
[10]Patent: US2004/266843,2004,A1 .Location in patent: Page 22.
[11]Journal of Medicinal Chemistry,2011,vol. 54,p. 166 - 178.
[12]ACS Medicinal Chemistry Letters,2012,vol. 3,p. 373 - 377.
[13]Organic Letters,2013,vol. 15,p. 5662 - 5665.
[14]Journal of Organic Chemistry,2016,vol. 81,p. 396 - 403.
[15]Angewandte Chemie - International Edition,2017,vol. 56,p. 3216 - 3220.
Angew. Chem.,2017,vol. 129,p. 3264 - 3268.
[16]Journal of Organic Chemistry,2018,vol. 83,p. 2425 - 2437.
[17]Chemical Communications,2018,vol. 54,p. 2494 - 2497.
[18]Patent: CN108689996,2018,A .Location in patent: Paragraph 0466; 0469; 0470; 0471; 0472.
[19]Chemistry - A European Journal,2019,vol. 25,p. 8245 - 8248.
[20]European Journal of Medicinal Chemistry,2019,vol. 178,p. 433 - 445.
[21]Chem,2020,vol. 6,p. 2994 - 3006.
[22]Chemistry - A European Journal,2021,vol. 27,p. 7738 - 7744.
[23]Bioorganic and medicinal chemistry,2002,vol. 10,p. 1229 - 1248.

5
[ 1189-71-5 ]
[ 2343-22-8 ]
C₉H₈ClFN₂O₃S [ No CAS ]

References: [1]Bioorganic and medicinal chemistry,2002,vol. 10,p. 1229 - 1248.

6
[ 2343-22-8 ]
[ 22980-09-2 ]
[ 861709-86-6 ]

References: [1]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 6073 - 6084.
[2]Tetrahedron Letters,2005,vol. 46,p. 1423 - 1425.

7
[ 49609-84-9 ]
[ 2343-22-8 ]
[ 931105-48-5 ]

Yield	Reaction Conditions	Operation in experiment
79%	With triethylamine; In acetonitrile; at 23℃; for 16h;	Example 22; 2-(4-(1H-Pyrrolo[2,3-b]pyridin-4-yloxy)-3-fluorophenylamino)pyridin-3-yl)(5-fluoroindolin-1-yl)methanone, dihydrochloride salt; A) (2-Chloropyridin-3-yl)-(5-fluoroindolin-1-yl)methanone; 2-Chloronicotinoyl chloride (200 mg, 1.14 mmol) was dissolved in CH3CN (5.6 mL). 5-Fluoroindoline (171 mg, 1.25 mmol) was added followed by triethylamine (0.24 mL, 1.71 mmol) and the reaction mixture was stirred at 23 C. for 16 h. The solvent was removed by evaporation and the residue was partitioned between CH2Cl2 (10 mL) and sat. aq. NaHCO3 solution (10 mL). The organic phase was removed and the aqueous phase was extracted with CH2Cl2 (2×10 mL). The combined organics were dried over Na2SO4 and concentrated in vacuo. Flash column chromatography (40 g SiO2, 2% CH3OH-CH2Cl2) afforded the desired product as an off-white solid (247.8 mg, 79%). 1H NMR (DMSO-d6) δ 3.14 (t, 2H, J=8.39 Hz), 3.82 (t, 2H, J=8.39 Hz), 7.09 (dt, 1H, J=9.03, 2.80 Hz,), 7.20 (dd, 1H, J=8.39, 2.80 Hz), 7.60 (dd, 1H, J=7.38, 4.83 Hz), 8.10 (dd, 1H, J=7.63, 2.03 Hz), 8.15 (dd, 1H, J=8.90, 4.83 Hz), 8.55 (dd, 1H, J=4.83, 1.78 Hz).

References: [1]Patent: US2007/78140,2007,A1 .Location in patent: Page/Page column 38.

8
[ 2343-22-8 ]
[ 98482-70-3 ]
[ 819076-55-6 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1486 - 1490.
[2]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1975 - 1980.

9
[ 2343-22-8 ]
benzyl (S)-1-oxopropan-2-ylcarbamate [ No CAS ]
[ 913180-81-1 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1975 - 1980.

10
[ 2343-22-8 ]
[ 75-36-5 ]
[ 2354-90-7 ]

References: [1]Advanced Synthesis and Catalysis,2015,vol. 357,p. 1149 - 1153.
[2]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 5818 - 5821.
[3]Chemistry - A European Journal,2014,vol. 20,p. 3606 - 3609.

11
[ 401564-36-1 ]
[ 2343-22-8 ]
3-[(2S,4S)-1-tert-butoxycarbonyl-4-(5-fluoro-1-indolinyl)-2-pyrrolidinylcarbonyl]-1,3-thiazolidine [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2007,vol. 15,p. 641 - 655.

12
[ 2343-22-8 ]
[ 1018819-67-4 ]
tert-butyl [3-(5-fluoro-2,3-dihydro-1H-indol-1-yl)propyl][(2S)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl}carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%		(8-Methyl-2,3-dihydro-[l,4]dioxino[2,3-f]quinolin-2-yl)-(3-oxo-propyl)- carbamic acid tert-butyl ester (Ic) (0.13g, 0.34 mmol) and <strong>[2343-22-8]5-fluoroindoline</strong> (0.19g, 1.4 mmol) were dissolved in MeOH and then treated with NaCNBH3 (0.19 g, 3.0 mmol) and AcOH (glacial; 0.2 mL). After approximately 2 hours, TLC indicated reaction was complete. The reaction mixture was carefully basified with 2.5M NaOH until pH~12. Then, the reaction mixture was extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, concentrated, and purified by silica gel chromatography to afford product as a near colorless oil (0.13Og, 76%); MS (ES) m/z = 508.3 [M+H]+.

References: [1]Patent: WO2008/42735,2008,A1 .Location in patent: Page/Page column 58.

13
[ 2343-22-8 ]
[ 5554-64-3 ]
[ 915953-61-6 ]