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Product Details of 2-Amino-6-fluoropyridine

CAS No. :1597-32-6
Formula : C5H5FN2
M.W : 112.11
SMILES Code : FC1=CC=CC(N)=N1
MDL No. :MFCD04114200
InChI Key :UZALKVXCOUSWSL-UHFFFAOYSA-N
Pubchem ID :2761399

Safety of 2-Amino-6-fluoropyridine

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Application In Synthesis of 2-Amino-6-fluoropyridine

* 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 [ 1597-32-6 ]

[ 1597-32-6 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 3282-30-2 ]
  • [ 1597-32-6 ]
  • [ 86847-87-2 ]
YieldReaction ConditionsOperation in experiment
93% With pyridine; at 0 - 20℃; N-(6-Fluoropyridin-2-yl)pivalamide. <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (13.1 g, 117 mmol) was dissolved in anhydrous pyridine (100 mL), and cooled to 0 C. followed by fast dropwise addition of trimethylacetyl chloride (15.9 mL, 129 mmol) over 2 min. 5 min later, the resulting slurry was stirred over night at room temperature. Partial of the solvent was removed on rotary vacuum. The residue was partitioned between saturated ammonium chloride (200 mL) and EtOAc (200 mL). After separation, the organic layer was washed with brine (50 mL), dried over MgSO4, concentrated on rotary vacuum, and purified on flash chromatography eluting with 2575% EtOAc/Hexanes (1400 mL) to afford the expected product as a white solid(21.4 g, 93% yield); 1H NMR (400 MHz, CDCl3) δ ppm 1.29 (s, 9H), 6.63 (dd, J=8.06, 2.01 Hz, 1H), 7.76 (q, J=8.14 Hz, 1H), 7.85 (s, 1H), 8.09 (dd, J=8.06, 1.76 Hz, 1H); Mass spec. 197.15 (MH+), Calc. for C10H13FN2O196.1
93% With pyridine; at 0 - 20℃; N-(6-Fluoropyridin-2-yl)pivalamide; <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (13.1 g, 117 mmol) was dissolved in anhydrous pyridine (100 mL), and cooled to 0 C. followed by fast dropwise addition of trimethylacetyl chloride (15.9 mL, 129 mmol) over 2 min. 5 min later, the resulting slurry was stirred over night at room temperature. Partial of the solvent was removed on rotary vacuum. The residue was partitioned between saturated ammonium chloride (200 mL) and EtOAc(200 mL). After separation, the organic layer was washed with brine (50 mL), dried over MgSO4, concentrated on rotary vacuum, and purified on flash chromatography eluting with 2575% EtOAc/Hexanes (1400 mL) to afford the expected product as a white solid(21.4 g, 93% yield); 1H NMR (400 MHz, CDCl3) δ ppm 1.29 (s, 9 H), 6.63 (dd, J=8.06, 2.01 Hz, 1 H), 7.76 (q, J=8.14 Hz, 1 H) ,7.85 (s, 1 H), 8.09 (dd, J=8.06, 1.76 Hz, 1 H); Mass spec. 197.15 (MH+), Calc. for C10H13FN2O196.1.
  • 2
  • [ 1513-65-1 ]
  • [ 1597-32-6 ]
YieldReaction ConditionsOperation in experiment
94% With ammonia; In water; at 105℃; for 15h; Example 13: (4S)-Λ/-Methyl-Λ/-(f5-(4-methyl-1-piperazinvnimidazoϖ .2-aloyridin-2- vϖmethyl)-3,4-dihvdro-2H-pyranof3,2-b1pyridin-4-arnine EPO <DP n="41"/>A) 6-Fluoro-2-pyridinamine: A solution of 2,6-difluoropyridine (50 g, 434 mmol) in ammonium hydroxide (200 mL, 28.0- 30.0%) was heated at 1050C in a steel bomb for 15 hours. The reaction was cooled in an ice bath and the precipitate filtered, rinsed with cold water, and dried to yield 6-fluoro-2- pyridinamine (45.8 g, 94% yield) as a white solid. 1H-NMR (CDCI3): δ 7.53 (m, 1 H)1 6.36 (dd, 1 H), 6.26 (dd, 1 H), 4.56 (s, 2H).
94% With ammonia; In water; at 105℃; for 15h; A solution of 2,6-difluoropyridine (50 g, 434 mmol) in ammonium hydroxide (200 mL, 28.0-30.0%) was heated at 1050C in a steel bomb for 15 hours. The reaction was cooled in an ice bath and the precipitate filtered, rinsed with cold water, and dried to yield 6-fluoro-2-pyridinamine (45.8 g, 94% yield) as a white solid. 1H-NMR (CDCI3): δ 7.53 (m, 1H), 6.36 (dd, 1H), 6.26 (dd, 1H), 4.56 (s, 2H).
94% With ammonia; In water; at 105℃; for 15h; A solution of 2,6-difluoropyridine (50 g, 434 mmol) in ammonium hydroxide (200 mL, 28.0-30.0%) was heated at 1050C in a steel bomb for 15 hours. The reaction was cooled in an ice bath and the precipitate filtered, rinsed with cold water, and dried to yield 6-fluoro-2-pyridinamine (45.8 g, 94% yield) as a white solid. 1H-NMR (CDCI3): δ 7.53 (m, 1 H), 6.36 (dd, 1 H), 6.26 (dd, 1 H), 4.56 (s, 2H).
94% With ammonia; In water; at 105℃; for 15h; A solution of 2,6-difluoropyridine (50 g, 434 mmol) in ammonium hydroxide (200 ml_, 28.0-30.0%) was heated at 1050C in a steel bomb for 15 hours. The reaction was cooled in an ice bath and the precipitate filtered, rinsed with cold water, and dried to yield 6-fluoro-2-pyridinamine (45.8 g, 94% yield) as a white solid. 1H-NMR (CDCI3): δ 7.53 (m, 1 H)1 6.36 (dd, 1 H), 6.26 (dd, 1 H), 4.56 (s, 2H).
94% With ammonia; In water; at 105℃; for 15h; A solution of 2,6-difluoropyridine (50 g, 434 mmol) in ammonium hydroxide (200 mL, 28.0-30.0%) was heated at 1050C in a steel bomb for 15 hours. The reaction was cooled in an ice bath and the precipitate filtered, rinsed with cold water, and dried to yield 6-fluoro-2-pyridinamine (45.8 g, 94% yield) as a white solid. 1H-NMR (CDCI3): δ 7.53 (m, 1H), 6.36 (dd, 1H), 6.26 (dd, 1H), 4.56 (S1 2H).
92% With ammonium hydroxide; In water; at 110℃; 2-(chloromethyl)-5-fluoroimidazoH ,2-alpyridine: 2,6-difluoropyridine (31.5 ml_, 0.348 mol) was diluted with 30% ammonium hydroxide(20OmL) in a steel bomb and heated to 110s C overnight. The bomb was cooled to room temperature over two hours then further cooled to 0Q C for two hours. The resulting solid was filtered and rinsed with water to obtain 26.39 g as a white solid. The filtrate was extracted with dichloromethane, dried over sodium sulfate and concentrated to afford an additional 9.3g (92% overall yield) of 6-fluoro-2- pyridinamine. A portion of the solid (5g, 0.044 mol) was dissolved in 1 ,2- dichloroethane (20 mL) and 1 ,3-dichloro-2-propanone (34.2 mL, 4.34 mol) was added in two portions. The reaction was stirred at 409 C over two days. The resulting solid was collected by filtration, dissolved in absolute ethanol (100 mL), and refluxed at 90Q C overnight. Solvent was evaporated and dichloromethane and saturated aqueous sodium bicarbonate was added to the residue. The aqueous layer was extracted two times with dichloromethane and once with a 3:1 chloroform: isopropanol mixture. Combined organics were dried over sodium sulfate and concentrated to a 3.61 g (62%) of 2-(chloromethyl)-5-fluoroimidazo[1 ,2-a]pyridine as a black oil which solidified upon standing. 1H NMR (400 MHz, DMSO-D6) δ 5.02 (s,2H), 7.29 (d, 1 H), 7.74 (d, 1 H), 7.88 (m, 1 H), 8.41 (s, 1 H); MS m/z 185 (M+1). EPO <DP n="47"/>B) 1 -[(5-fluoroimidazo[1 ,2-a]pyridin-2-yl)methyl]-1 ,2,3 ,4,4a,5,6,1 Ob-octahydro-1 ,10- phenanthroline:
82.6% Reference Example 58 Synthesis of 2-amino-6-fluoropyridine A solution of 30.0 g of 2,6-difluoropyridine in 150 mL (4.6 equivalents) was stirred in a sealed tube (inner pressure 12.1 kgcm-2) for 5 hours at 130 C. The reaction mixture was cooled to 0 C., which was left standing for two hours. Resulting crude crystals (plates) were collected by filtration with a glass filter, which were dried at 40 C. for 2 hours under reduced pressure (24.2 g, yield 82.6%). 1H-NMR (CDCl3, 300 MHz) δ: 4.33-4.74 (2H, br s), 6.20 (1H, m), 6.30 (1H, m), 7.48 (1H, m). Elemental analysis for C5H5H2F Calcd.: C, 53.57; H, 4.50; N, 24.97; F, 16.95 Found: C, 53.44; H, 4.45; N, 24.97; F, 17.25

  • 3
  • [ 1597-32-6 ]
  • [ 79-04-9 ]
  • [ 629616-84-8 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dichloromethane; at 20℃; for 5h; General procedure: choloro acetylcholoride (24mmol) and Et3N (24mmol) was added to a solution of 2-chloro-3-aminopyridine 7e (20mmol) in CH2Cl2 (20mL) at room temperature. The mixture was stirred for 5 hrs, and the solvent was evaporated under vacuum. The residue was purified by column chromatography (CH2Cl2:CH3OH: 30:1) on silica gel to obtain pure compound 8e as a white powder in 72% yield. To a solution of amide derivative 8e (5mmol) and potassium carbonate (7.5mmol) in acetonitrile (20ml) was added isothiocyanate (6mmol) during about 5min. The reaction mixture was stirred at room temperature overnight, and the solvent was evaporated under vacuum. The residue was extracted with ethyl acetate (20mL×3). The combined organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The obtained residue was purified by silica gel flash chromatography column (CH2Cl2:CH3OH: 30:1) to afford 5l as a white solid in 82% yield. To a solution of 5l (1mmol) in glacial acetic acid (5mL) were added aldehyde 6b (1mmol) and β-alanine (1mmol). The resulting mixture was stirred under reflux for 2h. Upon completion of the reaction, the mixture was cooled, the reaction was quenched with water, and the precipitate was filtered off, then the residue was purified by column chromatography (CH2Cl2:CH3OH: 15:1) on silica gel to obtain pure compound 2r as a faint yellow powder in 80% yield.
  • 4
  • [ 541-41-3 ]
  • [ 1597-32-6 ]
  • [ 1001070-25-2 ]
YieldReaction ConditionsOperation in experiment
68% With potassium carbonate; In acetonitrile; at 40℃; for 144h; To a solution containing 60 <strong>[1597-32-6]2-amino-6-fluoropyridine</strong> (5 g, 44.6 mmol, 1 eq.) in 30 CH3CN (110 ml) were added 63 K2CO4 (18.5 g, 133.8 mmol, 3 eq.) and 64 ethyl chloroformate (4.3 ml, 44.6 mmol, 1 eq.). The mixture was stirred at 40 C. for 4 days. Then, an additional portion of ethyl chloroformate (4.3 ml, 44.6 mmol, 1 eq.) was added and the mixture was stirred at 40 C. for 2 days. After returning to room temperature, 53 ethyl acetate was added and the organic phase was washed with a saturated solution of 54 NaHCO3, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography on silicagel (ethyl acetate/petroleum ether=10/90) to afford the desired product 65 13 in a yield of 68% (5.62 g). 1H NMR (400 MHz, CDCl3, 20 C.) δ 7.83 (dd, J=8.0 Hz, J=2.0 Hz, 1H), 7.77 (m, 1H), 7.45 (bs, 1H), 6.59 (m, 1H), 4.25 (q, J=8.0 Hz, 2H), 1.32 (t, J=8.0 Hz, 3H)
66.5% With potassium carbonate; In acetonitrile; at 40℃; for 144h; (R)-6-Fluoro-2-pyrrolidin-2-ylmethyl-1H-pyrrolo[2,3-b]pyridine. (Compound 47A) and (S)-6-Fluoro-2-pyrrolidin-2-ylmethyl-1H-pyrrolo[2,3-b]pyridine. (Compound 47B); Compound 55 (18 g, 161 mmol), 70 g K2CO3 (506 mmol) and 15.4 ml (161 mmol) ethyl-chloroformate were combined in CH3CN (400 ml) and stirred for 4 days at 40 C. TLC showed a moderate conversion. An additional 15.4 ml ethyl-chloroformate was added and stirring was continued for 2 days. The mixture was cooled. Ethyl acetate was added to the mixture and the organic layer was washed with a saturated NaHCO3 solution, dried (Na2SO4), filtered and concentrated. The resulting residue was purified by flash chromatography (diethyl ether/PE (1:3)) and afforded (6-fluoro-pyridin-2yl)-carbamic acid ethyl ester (56) (amorphous, 19.68 g, 66.5%). 1H-NMR (400 MHz, CDCl3): δ 7.83 (dd, J=8 Hz, 2 Hz, 1H), 7.80-7.73 (m, 1H), 7.50-7.40 (bs, 1H), 6.61-6.57 (m, 1H), 4.25 (q, J=8 Hz, 2H), 1.32 (t, J=8 Hz, 3H). (TLC diethyl ether/PE 1/1 Rf 0.5).
  • 5
  • [ 921-03-9 ]
  • [ 1597-32-6 ]
  • [ 878197-91-2 ]
YieldReaction ConditionsOperation in experiment
65% In 1,2-dimethoxyethane; at 85℃; for 15h; B) 2-(Dichloromethyl)-5-fluoroimidazoH .2-alpyridine: A solution of <strong>[1597-32-6]6-fluoro-2-pyridinamine</strong> (67 g, 0.60 mol) in ethylene glycol dimethyl ether (570 mL) was treated with 1 ,1 ,3-trichloroacetone (190 mL, 1.80 mol) and heated at 850C for 15 hours. The reaction was cooled in an ice bath and the precipitate filtered, rinsed with hexanes, and dried to yield 2-(dichloromethyl)-5-fluoroimidazo[1 ,2-a]pyridine (85 g, 65% yield) as an olive green solid. 1H-NMR (CDCI3): δ 8.18 (s, 1 H), 7.60 (s, 1 H), 7.54-7.46 (m, 2H), 6.93 (m, 1H).
65% In 1,2-dimethoxyethane; at 85℃; for 15h; A solution of <strong>[1597-32-6]6-fluoro-2-pyridinamine</strong> (67 g, 0.60 mol) in ethylene glycol dimethyl ether (570 mL) was treated with 1 ,1 ,3-trichloroacetone (190 mL, 1.80 mol) and heated at 850C for 15 hours. The reaction was cooled in an ice bath and the precipitate filtered, rinsed with hexanes, and dried to yield 2-(dichloromethyl)-5- fluoroimidazo[1 ,2-a]pyridine (85 g, 65% yield) as an olive green solid. 1H-NMR (CDCI3): δ 8.18 (s, 1 H), 7.60 (s, 1 H), 7.54-7.46 (m, 2H), 6.93 (m, 1 H).
65% In 1,2-dimethoxyethane; at 85℃; for 15h;Product distribution / selectivity; A solution of <strong>[1597-32-6]6-fluoro-2-pyridinamine</strong> (67 g, 0.60 mol) in ethylene glycol dimethyl ether (570 ml_) was treated with 1 ,1 ,3-trichloroacetone (190 mL, 1.80 mol) and heated at 850C for 15 hours. The reaction was cooled in an ice bath and the precipitate filtered, rinsed with hexanes, and dried to yield 2-(dichloromethyl)-5- fluoroimidazo[1 ,2-a]pyridine (85 g, 65% yield) as an olive green solid. 1H-NMR (CDCl3): δ 8.18 (s, 1H), 7.60 (s, 1H), 7.54-7.46 (m, 2H), 6.93 (m, 1H).
65% In 1,2-dimethoxyethane; at 85℃; for 15h; A solution of <strong>[1597-32-6]6-fluoro-2-pyridinamine</strong> (67 g, 0.60 mol) in ethylene glycol dimethyl ether (570 mL) was treated with 1 ,1 ,3-trichloroacetone (190 mL, 1.80 mol) and heated at 850C for 15 hours. The reaction was cooled in an ice bath and the precipitate filtered, rinsed with hexanes, and dried to yield 2-(dichloromethyl)-5- fluoroimidazo[1 ,2-a]pyridine (85 g, 65% yield) as an olive green solid. 1H-NMR (CDCI3): δ 8.18 (s, 1H), 7.60 (s, 1H), 7.54-7.46 (m, 2H), 6.93 (m, 1H).

  • 6
  • [ 1597-32-6 ]
  • [ 534-07-6 ]
  • [ 878198-71-1 ]
YieldReaction ConditionsOperation in experiment
77% In ethyl acetate; at 65℃; for 15h; E) 2-(Chloromethyl)-5-fluoroimidazoH ,2-alpyridine: A solution of <strong>[1597-32-6]6-fluoro-2-pyridinamine</strong> (6.7 g, 60 mmol) in ethyl acetate (30 ml_) was treated with 1 ,3-dichloroacetone (15 g, 120 mmol) dissolved in ethyl acetate (15 ml_) and heated at 650C for 15 hours. The reaction was cooled to room temperature and the precipitate filtered, rinsed with acetone and ether, and dried to yield a tan solid. This intermediate was dissolved in water and treated with saturated aqueous sodium bicarbonate until the pH = 7. The precipitate was collected by filtration and dried to yield 2-(chloromethyl)-5- fluoroimidazo[1 ,2-a]pyridine (1.9 g, 77% yield) as a tan solid. 1H-NMR (CDCI3): δ 7.68 (s, 1H), 7.42 (d, 1H), 7.26-7.20 (m, 1H), 6.47 (dd, 1H), 4.76 (s, 2H).
77% 2-(Chloromethyl)-5-fluoroimidazori ,2-alpyridine: A solution of <strong>[1597-32-6]6-fluoro-2-pyridinamine</strong> (6.7 g, 60 mmol) in ethyl acetate (30 ml_) was treated with 1 ,3-dichloroacetone (15 g, 120 mmol) dissolved in ethyl acetate (15 ml_) and heated at 650C for 15 hours. The reaction was cooled to room temperature and the precipitate filtered, rinsed with acetone and ether, and dried to yield a tan solid. This intermediate was dissolved in water and treated with saturated aqueous sodium bicarbonate until the pH = 7. The precipitate was collected by filtration and dried to yield 2-(chloromethyl)-5-fluoroimidazo[1 ,2-a]pyridine (1.9 g, 77% yield) as a tan solid. 1H-NMR (CDCI3): δ 7.68 (s, 1 H), 7.42 (d, 1 H), 7.26-7.20 (m, 1 H), 6.47 (dd, 1H), 4.76 (s, 2H).
62% In 1,2-dichloro-ethane; at 40℃; for 48h; 2-(chloromethyl)-5-fluoroimidazoH ,2-alpyridine: 2,6-difluoropyridine (31.5 ml_, 0.348 mol) was diluted with 30% ammonium hydroxide(20OmL) in a steel bomb and heated to 110s C overnight. The bomb was cooled to room temperature over two hours then further cooled to 0Q C for two hours. The resulting solid was filtered and rinsed with water to obtain 26.39 g as a white solid. The filtrate was extracted with dichloromethane, dried over sodium sulfate and concentrated to afford an additional 9.3g (92% overall yield) of 6-fluoro-2- pyridinamine. A portion of the solid (5g, 0.044 mol) was dissolved in 1 ,2- dichloroethane (20 mL) and 1 ,3-dichloro-2-propanone (34.2 mL, 4.34 mol) was added in two portions. The reaction was stirred at 409 C over two days. The resulting solid was collected by filtration, dissolved in absolute ethanol (100 mL), and refluxed at 90Q C overnight. Solvent was evaporated and dichloromethane and saturated aqueous sodium bicarbonate was added to the residue. The aqueous layer was extracted two times with dichloromethane and once with a 3:1 chloroform: isopropanol mixture. Combined organics were dried over sodium sulfate and concentrated to a 3.61 g (62%) of 2-(chloromethyl)-5-fluoroimidazo[1 ,2-a]pyridine as a black oil which solidified upon standing. 1H NMR (400 MHz, DMSO-D6) δ 5.02 (s,2H), 7.29 (d, 1 H), 7.74 (d, 1 H), 7.88 (m, 1 H), 8.41 (s, 1 H); MS m/z 185 (M+1). EPO <DP n="47"/>B) 1 -[(5-fluoroimidazo[1 ,2-a]pyridin-2-yl)methyl]-1 ,2,3 ,4,4a,5,6,1 Ob-octahydro-1 ,10- phenanthroline:
  • 7
  • [ 921-03-9 ]
  • [ 1597-32-6 ]
  • C8H8Cl2FN2O(1+)*Cl(1-) [ No CAS ]
YieldReaction ConditionsOperation in experiment
In 1,2-dimethoxyethane; at 20℃; for 15h; To a solution of <strong>[1597-32-6]6-fluoro-2-pyridinamine</strong> (Tetrahedron, 2002, 58, 489, incorporated by reference with regard to such) (2.8 g, 25 mmol) in ethylene glycol dimethyl ether (28 ml_) was added trichloroacetone (7.9 mL, 75 mmol). The mixture was stirred at room temperature for 15 hours and the resulting precipitate was collected by filtration and refluxed in ethyl alcohol (8 ml_) for 4 hours. The reaction mixture was cooled to room temperature, concentrated, dissolved in dichloromethane and washed with saturated aqueous sodium bicarbonate. The organic layer was isolated, dried with magnesium sulfate, and concentrated. The resulting solid was refluxed in aqueous calcium carbonate for 2 hours, cooled to room temperature, and extracted with dichloromethane. The organic layer was dried with magnesium sulfate and concentrated to give 1.4 g (34% yield) 5-fluoroimidazo[1,2-a]pyridine-2-carbaldehyde as a tan solid. 1H-NMR (CDCI3): δ 10.16 (s, 1 H), 8.22 (s, 1 H), 7.54 (d, 1 H), 7.34 (m, 1 H), 6.59 (m, 1 H); TLC (10% 2 M ammonia in methyl alcohol-ethyl acetate) Rf = 0.60.
  • 8
  • [ 1597-32-6 ]
  • [ 29209-30-1 ]
  • N-(6-fluoro-pyridin-2-yl)-3,4-dihydro-2-methyl-4-oxo-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide [ No CAS ]
YieldReaction ConditionsOperation in experiment
72.3% In 5,5-dimethyl-1,3-cyclohexadiene; (2) Synthesis of N-(6-fluoro-2-pyridyl)-3,4-dihydro-2-methyl-4-oxo-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide A mixture consisting of 7.68 g (0.0285 mole) of methyl 3,4-dihydro-2-methyl-4-oxo-2H-benzothiazine-3-carboxylate 1,1-dioxide, 4.8 g (0.0428 mole) of <strong>[1597-32-6]2-amino-6-fluoropyridine</strong>, and 29 ml of xylene was refluxed for 17 hours, during which the methanol formed by this reaction was continuously distilled off. After the mixture was cooled by allowing it to stand overnight, the resulting precipitate was separated by filtration. The filtrate was concentrated and then cooled to obtain an additional precipitate, which was combined with the previously obtained precipitate and washed with hot chloroform. Thus, 7.2 g of crystals having a melting point of 246-248 C. (decomp.) were obtained in a 72.3% yield. Elemental analysis--Calc.d for C15 H12 FN3 O4 S (mol. wt. 349.35): C, 51.55; H, 3.46; F, 5.44; N, 12.03; S, 9.18. Found: C, 51.69; H, 3.23; F, 5.55; N, 12.29; S, 9.14.
  • 9
  • [ 107-20-0 ]
  • 1N-HCl [ No CAS ]
  • [ 1597-32-6 ]
  • 5-fluoroimidazo[1,2-a]pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; In tetrahydrofuran; water; ethyl acetate; Reference Example 61 Synthesis of 5-fluoroimidazo[1,2-a]pyridine 2-Amino-6-fluoropyridine (12 g) was completely dissolved in 120 mL of distilled water at 60 C. To the solution was added 35 mL (2 equivalents) of 40% chloroacetaldehyde. The mixture was stirred for 3 hours at 60 C. The reaction mixture was gradually cooled to room temperature, to which were added a 1N-HCl aqueous solution (50 mL) and ethyl acetate (150 mL). The ethyl acetate solution was subjected to extraction with a 1N-HCl aqueous solution (100 mL). The extract was mixed with the aqueous solution. To this aqueous solution was added NaHCO3 for neutralization (pH 0.35-7.30). To the neutralized aqueous solution was added a mixture of ethyl acetate and THF (4:1) (150 mL*3) to extract the product. The extract solutions were combined and dried over anhydrous magnesium sulfate, which was concentrated under reduced pressure to afford 5-fluoroimidazo[1,2-a]pyridine as a black liquid product (9.5 g, yield 65%). 1H-NMR (CDCl3, 300 MHz) δ: 6.52 (1H, m), 7.26 (1H, m), 7.49 (2H, d, J=9.1 Hz), 7.66 (2H, m). MS (SIMS), 137(MH+).
  • 10
  • [ 918-00-3 ]
  • [ 1597-32-6 ]
  • [ 878197-67-2 ]
YieldReaction ConditionsOperation in experiment
34% To a solution of <strong>[1597-32-6]6-fluoro-2-pyridinamine</strong> (Tetrahedron, 2002, 58, 489, incorporated by reference with regard to such) (2.8 g, 25 mmol) in ethylene glycol dimethyl ether (28 mL) was added trichloroacetone (7.9 mL, 75 mmol). The mixture was stirred at room temperature for 15 hours and the resulting precipitate was collected by filtration and refluxed in ethyl alcohol (8 mL) for 4 hours. The reaction mixture was cooled to room temperature, concentrated, dissolved in dichloromethane and washed with saturated aqueous sodium bicarbonate. The organic layer was isolated, dried with magnesium sulfate, and concentrated. The resulting solid was refluxed in aqueous calcium carbonate for 2 hours, cooled to room temperature, and extracted with dichloromethane. The organic layer was dried with magnesium sulfate and EPO <DP n="46"/>concentrated to give 1.4 g (34% yield) 5-fluoroimidazo[1 ,2-a]pyridine-2-carbaldehyde as a tan solid. 1H-NMR (CDCI3): δ 10.16 (s, 1 H), 8.22 (s, 1 H), 7.54 (d, 1 H), 7.34 (m, 1 H), 6.59 (m, 1 H); TLC (10% 2 M ammonia in methyl alcohol-ethyl acetate) Rf = 0.60.
  • 11
  • [ 918-00-3 ]
  • [ 1597-32-6 ]
  • [ 878197-91-2 ]
YieldReaction ConditionsOperation in experiment
65% In diethylene glycol dimethyl ether; at 85℃; for 15h; A solution of <strong>[1597-32-6]6-fluoro-2-pyridinamine</strong> (67 g, 0.60 mol) in ethylene glycol dimethyl ether (570 mL) was treated with trichloroacetone (190 mL, 1.80 mol) and heated at 850C for 15 hours. The reaction was cooled in an ice bath and the precipitate filtered, rinsed with hexanes, and dried to yield 2-(dichloromethyl)-5-fluoroimidazo[1 ,2- a]pyridine (85 g, 65% yield) as an olive green solid. 1H-NMR (CDCI3): δ 8.18 (s, 1 H), 7.60 (s, 1 H), 7.54-7.46 (m, 2H), 6.93 (m, 1H).
  • 12
  • [ 921-03-9 ]
  • [ 1597-32-6 ]
  • [ 878197-67-2 ]
YieldReaction ConditionsOperation in experiment
34% To a solution of <strong>[1597-32-6]6-fluoro-2-pyridinamine</strong> (Tetrahedron, 2002, 58, 489, incorporated by reference with regard to such) (2.8 g, 25 mmol) in ethylene glycol dimethyl ether (28 mL) was added trichloroacetone (7.9 mL, 75 mmol). The mixture was stirred at room temperature for 15 hours and the resulting precipitate was collected by filtration and refluxed in ethyl alcohol (8 mL) for 4 hours. The reaction mixture was cooled to room temperature, concentrated, dissolved in dichloromethane and washed with saturated aqueous sodium bicarbonate. The organic layer was isolated, dried with magnesium sulfate, and concentrated. The resulting solid was refluxed in aqueous calcium carbonate for 2 hours, cooled to room temperature, and extracted with dichloromethane. The organic layer was dried with magnesium sulfate and concentrated to give 1.4 g (34% yield) 5-fluoroimidazo[1 ,2-a]pyridine-2-carbaldehyde as a tan solid. 1H-NMR (CDCI3): δ 10.16 (s, 1H), 8.22 (s, 1 H), 7.54 (d, 1H), 7.34 (m, 1H), 6.59 (m, 1H); TLC (10% 2 M ammonia in methyl alcohol-ethyl acetate) Rf = 0.60.
  • 13
  • [ 1597-32-6 ]
  • [ 944401-65-4 ]
YieldReaction ConditionsOperation in experiment
91% With N-Bromosuccinimide; In acetonitrile; at 0℃; for 3.0h;Inert atmosphere; A solution of commercially available 6-fluoro-pyridin-2-ylamine (1.0 g, 8.74 mmol, leq.) in acetonitrile (44 mL), protected from light and under nitrogen atmosphere, was set stirring at 0C before adding a solution of N-bromosuccinimide (0.79 g, 8.74 mmol, leq.) in acetonitrile (19 mL) over 30 min. After complete addition, the resulting solution was stirred for an additional 2h30. The reaction mixture was then concentrated under reduced pressure and the residue was dissolved in EtOAc, successively washed with brine and water. The organic layer was dried over Na2S04, filtered and concentrated in vacuo. The crude material was purified by flash column chromatography using a gradient of 25 % to 50 % EtOAc in heptane to give 5-bromo- 6-fluoro-pyridin-2-ylamine (1.45 g, 91%) as a white solid.H-NMR (400 MHz, CDCI3): d 7.55 (t, J= 8.6 Hz, 1H), 6.22 (dd, J= 8.3 Hz, 1.5 Hz, 1H), 4.70 (bs, 2H).13C-NMR (101 MHz, CDC ): d 158.8 (d, J= 235 Hz), 156.7 (d, J= 16 Hz), 144.9 (d, J= 2.9 Hz), 106.7 (d, J= 5.0 Hz), 89.4 (d, J= 38 Hz).
79% With N-Bromosuccinimide; In acetonitrile; at 20℃; for 72.0h;Darkness; Cooling with ice; 6-fluoropyridine-2-amine (2.40g) was dissolved in acetonitrile (45mL), the absence of light. Under ice-cooling N- bromosuccinimide (3.81 g) was added, the dark, for 3 days and nights stirred at room temperature. After the reaction mixture was concentrated to dryness and the resulting solid was purified by silica gel column chromatography to give the title compound 3.22g (79%).
72% With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; In N,N-dimethyl-formamide; at 0 - 33℃; for 6.0h; Add 2-amino-6-fluoropyridine (17.2g, 150mmol, 1eq.) To the reaction flask, 200ml N, N-dimethylformamide, Cool to 0 C. 1,3-dibromo-5,5-dimethylhydantoin (48.1g, 165mmol, 1.1eq.) Soluble in 150ml N, N-dimethylformamide, Then add dropwise to the above reaction system, Reaction at 33 C for 6 hours. After the reaction was completed, 350 ml of water was added to the reaction liquid, and a large amount of white solid precipitated. After stirring for 20 minutes, it was filtered and the filter cake was washed with water. The filter cake was vacuum dried to obtain 21.1 g of off-white solid 2-amino-5-bromo-6-fluoropyridine in 72% yield.
64.56% With N-Bromosuccinimide; In acetonitrile; at 25℃; for 6.0h; Into a lOOO-mL round-bottom flask, was placed 6-fluoropyridin-2-amine (30 g, 267.601 mmol, 1 equiv), CH ,CN (500 mL), NBS (52 g, 292.161 mmol, 1.09 equiv). The resulting solution was stirred for 6 hr at 25 degrees C. The resulting solution was diluted with 1000 mL of water. The resulting solution was extracted with 3x500 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2 x2000 ml of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product was re-crystallized from PE:EA in the ratio of 5:1. The solids were collected by filtration. This resulted in 33 g (64.56%) of 5- bromo-6-fluoropyridin-2-amine as a white solid. 1H NMR (300 MHz, Chlorofom /, ppm) d 7.61 (t, / = 8.6 Hz, 1H), 6.28 (dd, / = 8.3, 1.4 Hz, 1H), 4.45 (s, 2H).
40% With N-Bromosuccinimide; In chloroform; at 20℃; for 16.0h; To a 250 mL round bottom flask, were added 6-fluoro-2-aminopyridine (3 g, 0.0267 mol) and chloroform (90 mL). To the same flask, N-bromosuccinimide (5 g, 0.028 mol) was added. The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with chloroform and washed with water. The organic layer was separated, washed with brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to get the title compound [2 g, 40 %]. *H NMR (300 MHz, CDC13): delta 7.62 (t, = 9.0 Hz, 1H), 6.27 (m, 1H), 4.58 (s, 2H); LC-MS: 193.1 [M+2H]+.
22% [0269] To a solution of 6-fluoro-2-pyridylamine (1.0 g, 8.93 mmol) in chloroform(55 mL) was added N-bromosuccinimide (1.59 g, 8.93 mmol). The solution was stirred in the dark for 15 hours, at which time it was added to CH2Cl2 (200 mL) and IN NaOH (50 mL). Upon mixing, the layers were separated and the organic layer was washed with NaCl(sat.) (50 mL), dried over Na2SO4, filtered and concentrated. The crude material was purified by SiO2 chromatography (25% EtOAc/ hexanes) yielding 5-bromo-6-fluoro-2- pyridylamine (386 mg, 22%). LCMS (m/z): 190.9/192.9 (MH+); 1HNMR (CDCl3): delta 7.59 (t, J= 8.7 Hz, IH), 6.25 (dd, J= 8.1, 1.2 Hz, IH), 4.58 (bs, IH).
22% Synthesis o -bromo-6-fluoro-2-pyridylamine [00108] To a solution of 6-fluoro-2 -pyridylamine (1.0 g, 8.93 mmol) in chloroform (55 mL) was added N-bromosuccinimide (1.59 g, 8.93 mmol). The solution was stirred in the dark for 15 hours, at which time it was added to CH2CI2 (200 mL) and IN NaOH(50 mL). Upon mixing, the layers were separated and the organic layer was washed with NaCl(Sat.) (50 mL), dried over Na2S04, filtered and concentrated. The crude material was purified by Si02 chromatography (25% EtOAc/ hexanes) yielding 5-bromo-6-fiuoro-2- pyridylamine (386 mg, 22%). LCMS (m/z): 190.9/192.9 (MH ); ¾ NMR (CDC13): delta 7.59 (t, J = 8.7 Hz, 1H), 6.25 (dd, J= 8.1, 1.2 Hz, 1H), 4.58 (bs, 1H).
With N-Bromosuccinimide; In acetonitrile; for 4.0h; To a stirred solution of 6-fluoro-pyridin-2-ylamin (1.0 g, 8.93 mmol) in acetonitrile (50 mL), protected from light and under nitrogen atmosphere, N-bromosuccinimide (0.79 g, 4.46 mmol) was added. After 1 hour, an additional portion of N-bromosuccinimide (0.79 g, 4.46 mmol) was added and the stirring was continued for 3 hours. The volatiles were removed under reduced pressure and the crude material was purified by flash column chromatography using a gradient of 25% to 30% ethyl acetate in hexane to give 5-bromo-6-fluoro-pyridin-2-ylamine (1.45 g) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) delta: 7.60 (t, J=8.59 Hz, 1H) 6.15-6.36 (m, 1H) 4.58 (br. s., 2H) ESMS: m/z 193.34 [M+1]+ for 81Br isotope
With N-Bromosuccinimide; In acetonitrile; at 10 - 20℃; for 1.5h; NBS (50. Og, 280.99mmol) was added slowly to 6-fluoropyridin-2-amine (30g, 267.61mmol) in MeCN (300mL) cooled to 10-20C over a period of 30 minutes. The resulting solution was stirred at ambient temperature for 60 minutes then the solvent removed under reduced pressure. The residue was diluted with water, the precipitate collected by filtration, washed with water (200mL) and dried under vacuum to afford the desired material (50. Og, 98%) as a white solid, which was used without further purification. NMR Spectrum: 1H MR (300MHz, DMSO-d6) delta 6.29 (1H, d), 6.57 (2H, bs), 7.65 (1H, t). Mass Spectrum: m/z (ES+)[M+H]+ = 191.
With N-Bromosuccinimide; In acetonitrile; at 10 - 30℃; for 1.5h;Inert atmosphere; NBS (50. Og, 280.99mmol) was added slowly to 6-fluoropyridin-2-amine (30 g, 267.61 mmol) in MeCN (300 mL) cooled to 10-20C over a period of 30 minutes. The resulting solution was stirred at ambient temperature for 60 minutes then the solvent removed under reduced pressure. The residue was diluted with water, the precipitate collected by filtration, washed with water (200 mL) and dried under vacuum to afford the desired material (50.0 g, 98%) as a white solid, which was used without further purification. NMR Spectrum: JH NMR (300MHz, DMSO-d6) delta 6.29 (1H, d), 6.57 (2H, bs), 7.65 (1H, t). Mass Spectrum: m z (ES+)[M+H]+ = 191.
With N-Bromosuccinimide; Example 59 Synthesis of 6-fluoropyridin-2-amine. A mixture of 6-fluoropyridin-2-amine (3 g, 26.8 mmol) and N-bromosuccinimide (5.25 g, 29.5 mmol) in dry CH3CN (20 mL) was stirred at 0 C. for 2 h. Water (100 mL) was added and the mixture was extracted with EtOAc (100 mL*3). The combined organic layers were concentrated and purified by silica gel chromatography (EA/PE=1/5) to give 5-bromo-6-fluoropyridin-2-amine (4.31 g, yield: 84.2%) as a white solid. ESI-MS [M+H]+: 191.0.

  • 14
  • [ 1097180-24-9 ]
  • [ 1597-32-6 ]
  • [ 1097264-67-9 ]
  • C18H24FN3O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
In N,N-dimethyl-formamide; at 80℃; for 2.5h; To a solution of 1,1-dimethylethyl (2S)-2-(3-bromo-2-oxopropyl)-1-piperidinecarboxylate D2 (0.11 g, 0.26 mmol) in DMF (1 ml) was added <strong>[1597-32-6]6-fluoro-2-pyridinamine</strong> (0.029 g, 0.26 mmol) and the mixture was stirred at 80 C. for 2.5 h. The reaction mixture was eluted through a SCX column. Collected fractions gave 0.032 g of an oil containing a mixture of the title compound, the corresponding N-Boc protected derivative and some residual <strong>[1597-32-6]6-fluoro-2-pyridinamine</strong>. [N-Boc derivative data. LC-MS: rt=1.54 min, peak observed: 334 (M+1). C18H24FN3O2 requires 333]. The crude was dissolved in DCM (2.50 ml) and the resulting solution cooled to 0 C. TFA (0.50 ml) was added dropwise, the reaction left under stirring for 1 h and then eluted through a SCX column. Collected fractions gave the title compound D22 (0.020 g) contaminated with <strong>[1597-32-6]6-fluoro-2-pyridinamine</strong>. The material was used without further purification in the next step.HPLC (walk-up): rt=1.50 min. MS: (ES/+) m/z: 234 (M+1). C13H16FN3 requires 233.
  • 15
  • [ 1147216-22-5 ]
  • [ 1597-32-6 ]
  • [ 1187324-63-5 ]
YieldReaction ConditionsOperation in experiment
35% Compound 20: 1-(4-Fluorophenyl)-/V-(6-fluoro-2-pyridinyl)-5-methyl-1H-1 ,2,3-triazole- 4-carboxamide; To a solution of <strong>[1597-32-6]6-fluoro-2-pyridinamine</strong> (0.092 g, 0.822 mmol) in dry 1 ,4-dioxane (1 ml) was added dropwise trimethylaluminium (0.401 ml, 0.802 mmol) (2M solution in <n="41"/>toluene). The solution was stirred at room temperature for 30 min. Then a solution of ethyl 1-(4-fluorophenyl)-5-methyl-1 H-1 ,2,3-triazole-4-carboxylate (Intermediate 2) (0.05 g, 0.201 mmol) in dry 1 ,4-dioxane (1 ml) was added at room temperature and the reaction was heated to 100 0C for 1.5 hours. The reaction was cooled to room temperature, quenched cautiously with water (0.06 ml), and stirred at room temperature for 10 min. Then, sodium sulphate (0.25 g) was added to bind the water and the mixture was stirred vigorously for 5 min. Dichloromethane was added and the mixture was stirred for an additional 10 min at room temperature. The solution was filtered and the solid was washed with dichloromethane. The filtrate was evaporated to afford a residue. The residue was partially dissolved in methanol, filtered and the solid washed with diethyl ether to afford a the title compound (44.5%); MH+= 316; 1HNMR (DMSO, 400 MHz): 2.57 (3H s), 6.96 (1 H m), 7.53 (2H t), 7.76 (2H m), 8.07 (2H m), 10.22 (1 H s).
  • 16
  • [ 884494-73-9 ]
  • [ 1597-32-6 ]
  • [ 1196661-96-7 ]
YieldReaction ConditionsOperation in experiment
With triethylsilane; trifluoroacetic acid; In acetonitrile; at 80℃; for 4h; To 6-fluoro-pyridin-2ylamine (14, 1.50 g, 13.4 mmol) in 52.9 mL of acetonitrile, <strong>[884494-73-9]5-fluoro-6-methoxy-pyridine-3-carbaldehyde</strong> (23, 2.00 g, 12.9 mmol), triethylsilane (10.6 mL, 66.3 mmol), and trifluoroacetic acid (5.3 mL, 69.0 mmol) were added. The reaction was stirred at 80 C. overnight, then concentrated under vacuum, combined with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography, eluting with 15-100% ethyl acetate in hexane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound as white solid (24, 3.21 g).
3.21 g With triethylsilane; trifluoroacetic acid; In acetonitrile; at 80℃; To 6-fluoro-pyridin-2-ylamine (43, 1.50 g, 13.4 mmol) in 52.9 mL of acetonitrile, <strong>[884494-73-9]5-fluoro-6-methoxy-pyridine-3-carbaldehyde</strong> (57, 2.00 g, 12.9 mmol), triethylsilane (10.6 mL, 66.3 mmol), and trifluoroacetic acid (5.3 mL, 69.0 mmol) were added. The reaction was stirred at 80 C. overnight, then concentrated under vacuum, combined with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography, eluting with 15-100% ethyl acetate in hexane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound as white solid (58, 3.21 g).
  • 17
  • [ 89-98-5 ]
  • [ 1597-32-6 ]
  • [ 1196661-93-4 ]
YieldReaction ConditionsOperation in experiment
To <strong>[1597-32-6]6-fluoro-pyridin-2-ylamine</strong> (14, 2.47 g, 22.0 mmol) in 60.0 mL of acetonitrile, 2-chloro-benzaldehyde (15, 3.09 g, 22.0 mmol), triethylsilane (14.0 mL, 87.6 mmol) and trifluoroacetic acid (7.00 mL, 90.9 mmol) were added. The reaction was stirred at 80 C. for 4 hours, then solvents removed under vacuum, and the residue was combined with aqueous potassium carbonate and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered and the filtrate concentrated under vacuum to provide the desired compound, which was used in the next step without further purification. MS (ESI) [M+H+]+=272.1.
With triethylsilane; trifluoroacetic acid; In acetonitrile; at 80℃; for 4h; To <strong>[1597-32-6]6-fluoro-pyridin-2-ylamine</strong> (43, 2.47 g, 22.0 mmol) in 60.0 mL of acetonitrile, 2-chloro-benzaldehyde (44, 3.09 g, 22.0 mmol), triethylsilane (14.0 mL, 87.6 mmol) and trifluoroacetic acid (7.00 mL, 90.9 mmol) were added. The reaction was stirred at 80 C. for 4 hours, then solvents removed under vacuum, and the residue was combined with aqueous potassium carbonate and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered and the filtrate concentrated under vacuum to provide the desired compound, which was used in the next step without further purification. MS (ESI) [M+H+]+=272.1.
  • 18
  • [ 4364-02-7 ]
  • [ 1597-32-6 ]
  • [ 1208372-58-0 ]
YieldReaction ConditionsOperation in experiment
~ 10% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; at 20℃;Cooling with ice; To a stirred and ice-cooled solution of 2-(4-methoxy-phenyl)-quinoline-4-carboxylic acid (INT-2; 2.500 g, 8.9512 mmol) and <strong>[1597-32-6]6-fluoro-pyridin-2-ylamine</strong> (1 .204 g, 10.7414 mmol) in dichloromethane (30 ml), triethylamine (6.340 g, -8.7 ml, 62.6584 mmol) is added, followed by portion-wise addition of 1 - propanephosphonic acid cyclic anhydride (22.785 g, 35.8048 mmol) and the mixture is allowed to attain room temperature spontaneously overnight. The resulting mixture is diluted with dichloromethane (-40 ml), washed with water and brine, dried (MgSO4), and evaporated to afford a reddish gummy residue (3.350 g, 100% mass balance). This is purified by column chromatography eluting with 12- 16% ethyl acetate in hexane, to obtain the title compound as a pale yellow solid (0.320 g, -10% yield). M.p. 174.4-175.7C.
~ 10% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; at 20℃;Cooling with ice; To a stirred and ice-cooled solution of 2-(4-methoxy-phenyl)-quinoline-4-carboxylic acid (INT-2; 2.500 g, 8.9512 mmol) and <strong>[1597-32-6]6-fluoro-pyridin-2-ylamine</strong> (1.204 g, 10.7414 mmol) in dichloromethane (30 ml), triethylamine (6.340 g, 8.7 ml, 62.6584 mmol) is added, followed by portion-wise addition of 1-propanephosphonic acid cyclic anhydride (22.785 g, 35.8048 mmol) and the mixture is allowed to attain room temperature spontaneously overnight. The resulting mixture is diluted with dichloromethane (40 ml), washed with water and brine, dried (MgSO4), and evaporated to afford a reddish gummy residue (3.350 g, 100% mass balance). This is purified by column chromatography eluting with 12-16% ethyl acetate in hexane, to obtain the title compound as a pale yellow solid (0.320 g, 10% yield). M.p. 174.4-175.7 C.
  • 19
  • [ 133676-16-1 ]
  • [ 1597-32-6 ]
  • [ 1208372-60-4 ]
YieldReaction ConditionsOperation in experiment
~ 11% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; at 20℃;Cooling with ice; To a stirred and ice-cooled solution of 2-(3,4-dimethoxy-phenyl)- quinoline-4-carboxylic acid (INT-3; 2.000 g, 6.4658 mmol) and 6-fluoro-pyridin-2- ylamine (0.870 g, 7.759 mmol) in dichloromethane (20 ml), triethylamine (4.580 g,-15.4 ml, 45.2606 mmol) is added, followed by portion-wise addition of 1 - propanephosphonic acid cyclic anhydride (16.458 g, 25.8632 mmol) and the mixture is allowed to attain room temperature spontaneously overnight and stirred at this temperature for additional 20 hours. The resulting mixture is diluted with dichloromethane (-50 ml), washed with water and brine, dried (MgSO4), and evaporated to afford a brown gummy residue (2.600 g, 100% mass balance). This is purified by column chromatography eluting with 32-36% ethyl acetate in hexane, to obtain the title compound as a pale yellow solid (0.300 g, -11 % yield). M. p. 225.2-226.4C.
~ 11% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; at 20℃;Cooling with ice; To a stirred and ice-cooled solution of 2-(3,4-dimethoxy-phenyl)-quinoline-4-carboxylic acid (INT-3; 2.000 g, 6.4658 mmol) and <strong>[1597-32-6]6-fluoro-pyridin-2-ylamine</strong> (0.870 g, 7.759 mmol) in dichloromethane (20 ml), triethylamine (4.580 g, 15.4 ml, 45.2606 mmol) is added, followed by portion-wise addition of 1-propanephosphonic acid cyclic anhydride (16.458 g, 25.8632 mmol) and the mixture is allowed to attain room temperature spontaneously overnight and stirred at this temperature for additional 20 hours. The resulting mixture is diluted with dichloromethane (50 ml), washed with water and brine, dried (MgSO4), and evaporated to afford a brown gummy residue (2.600 g, 100% mass balance). This is purified by column chromatography eluting with 32-36% ethyl acetate in hexane, to obtain the title compound as a pale yellow solid (0.300 g, 11% yield). M.p. 225.2-226.4 C.
  • 20
  • [ 5466-31-9 ]
  • [ 1597-32-6 ]
  • [ 1208372-55-7 ]
YieldReaction ConditionsOperation in experiment
~ 18% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; at 20℃;Cooling with ice; To a stirred and ice-cooled solution of commercial 2-(4-chloro-phenyl)- quinoline-4-carboxylic acid (1.400 g, 4.9346 mmol) and 2-amino-6-fluoropyhdine (0.664 g, 5.9215 mmol) in dichloromethane (20 ml), triethylamine (3.495 g, -4.8 ml, 34.5422 mmol) is added, followed by portion-wise addition of 1 - propanephosphonic acid cyclic anhydride (12.561 g, 19.7384 mmol) and the mixture is allowed to attain room temperature spontaneously overnight. The resulting mixture is diluted with dichloromethane (-30 ml), washed with water and brine, dried (MgSO4), and evaporated to afford a brown gummy residue (1.860 g, 100% mass balance). This is purified by column chromatography eluting with 8% ethyl acetate in hexane, to obtain the title compound as a pale yellow solid (0.474 g, -18% yield). M.p. 200-2010C.
~ 18% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; at 20℃;Cooling with ice; To a stirred and ice-cooled solution of commercial 2-(4-chloro-phenyl)-quinoline-4-carboxylic acid (1.400 g, 4.9346 mmol) and <strong>[1597-32-6]2-amino-6-fluoropyridine</strong> (0.664 g, 5.9215 mmol) in dichloromethane (20 ml), triethylamine (3.495 g, 4.8 ml, 34.5422 mmol) is added, followed by portion-wise addition of 1-propanephosphonic acid cyclic anhydride (12.561 g, 19.7384 mmol) and the mixture is allowed to attain room temperature spontaneously overnight. The resulting mixture is diluted with dichloromethane (30 ml), washed with water and brine, dried (MgSO4), and evaporated to afford a brown gummy residue (1.860 g, 100% mass balance). This is purified by column chromatography eluting with 8% ethyl acetate in hexane, to obtain the title compound as a pale yellow solid (0.474 g, 18% yield). M.p. 200-201 C
  • 21
  • [ 148887-61-0 ]
  • [ 1597-32-6 ]
  • [ 1208372-52-4 ]
YieldReaction ConditionsOperation in experiment
9.53% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; at 20℃;Cooling with ice; 4-carboxylic acid (INT-1 ; 7.000 g, 22.0016 mmol) and 2-amino-6-fluoropyhdine (2.467 g, 22.0016 mmol) in dichloromethane (200 ml), triethylamine (15.584 g, -21.5 ml, 154.0112 mmol) is added, followed by portion-wise addition of 1 - propanephosphonic acid cyclic anhydride (37.803 g, 59.4043 mmol) and the mixture is allowed to attain room temperature spontaneously overnight. The resulting mixture is concentrated (-100 ml), washed with water and brine, dried (MgSO4), and evaporated to afford a brown gummy residue (9.100 g, 100% mass balance). This is purified by column chromatography eluting with 8% ethyl acetate in hexane, to obtain the title compound as an orange solid (0.865 g, 9.53% yield). M.p. 204.2-205.50C.
9.53% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; at 20℃;Cooling with ice; To a stirred and ice-cooled solution of 2-(3,4-dichloro-phenyl)-quinoline-4-carboxylic acid (INT-1; 7.000 g, 22.0016 mmol) and <strong>[1597-32-6]2-amino-6-fluoropyridine</strong> (2.467 g, 22.0016 mmol) in dichloromethane (200 ml), triethylamine (15.584 g, 21.5 ml, 154.0112 mmol) is added, followed by portion-wise addition of 1-propanephosphonic acid cyclic anhydride (37.803 g, 59.4043 mmol) and the mixture is allowed to attain room temperature spontaneously overnight. The resulting mixture is concentrated (100 ml), washed with water and brine, dried (MgSO4), and evaporated to afford a brown gummy residue (9.100 g, 100% mass balance). This is purified by column chromatography eluting with 8% ethyl acetate in hexane, to obtain the title compound as an orange solid (0.865 g, 9.53% yield). M.p. 204.2-205.5 C
  • 22
  • [ 405175-13-5 ]
  • [ 1597-32-6 ]
  • [ 898195-98-7 ]
  • 23
  • [ 1355324-97-8 ]
  • [ 1597-32-6 ]
  • [ 1355326-84-9 ]
YieldReaction ConditionsOperation in experiment
41.52% With sodium iodide; In acetone; at 70℃; Example 3. Preparation of Compound 302. Compound 302 was also synthesized via Scheme 2 using the following protocol.To a solution of Compound 118 (400mg, 0.96 mmol) in acetone (10 ml) was added 6- Fluoro-pyridin-2-ylamine (269 mg, 2.4mmol) and Nal (288 mg, 1.92mmol). The reaction mixture was stirred at 70C overnight. The resulting mixture was concentrated in vacuo and DCM (20 ml) was added. The organic solution was washed with water, brine, dried over Na2S04 and filtered. The solvent was evaporated in vacuo. The residue was purified by prep- TLC to give the desired product as a white solid (196 mg, 41.52% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.02 (s, IH), 7.83 (br, IH), 7.52-7.46 (m, IH), 7.33-7.02 (m, 5H), 6.86 (s, IH), 6.72-6.65 (m, 2H), 6.48-6.47 (d, IH, J=7.2), 6.23 (s, IH), 6.12-6.10 (d, IH, J=6.8), 3.86-3.83 (d, IH, J=13.6), 3.62-3.61 (d, IH, J=6), 3.49-3.41 (m, IH), 2.38 (s, 3H), 1.70-1.52 (m, 5H), 1.25- 0.96 (m, 5H); MS: 493.1 (M+l) +.
  • 24
  • [ 110-89-4 ]
  • [ 1597-32-6 ]
  • [ 4945-46-4 ]
YieldReaction ConditionsOperation in experiment
94% at 205℃; for 0.5h;Microwave irradiation; A suspension of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (500 mg, 4.4 mmol), piperidine (1.4 mL, 14.1 mmol) in water (0.5 mL) was heated to 205 C. in a microwave oven for 30 minutes. The reaction mixture was purified by chromatography (silica gel, 200-300 mesh, petroleum ether:ethyl acetate=3:1) to give 6-(piperidin-1-yl)pyridin-2-amine (740 mg, 94%) as a light yellow oil. LC-MS: [M+H]+, 178.1, tR=0.974 min.
94% In water; at 205℃; for 0.5h;Microwave irradiation; A suspension of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (500 mg, 4.4 mmol), piperidine (1.4 mL , 14.1 mmol) in water (0.5 mL) was heated to 205 C in a microwave oven for 30 minutes. The reaction mixture was purified by chromatography (silica gel, 200 - 300 mesh, petroleum ether : ethyl acetate = 3 : 1) to give 6-(piperidin-l-yl)pyridin-2-amine(740 mg, 94 %) as a light yellow oil. LC-MS : [M+H]+, 178.1 , tR = 0.974min.
  • 25
  • [ 1597-32-6 ]
  • [ 765-38-8 ]
  • [ 1415695-18-9 ]
YieldReaction ConditionsOperation in experiment
With potassium fluoride; copper diacetate; potassium carbonate; In dimethyl sulfoxide; at 20 - 150℃; for 4h; Step 36-(2-Methylpyrrolidin-1-yl)pyridin-2-amine Procedure:To a stirred solution of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (0.224 g, 1 mmol) and 2-methylpyrrolidine (0.173 g, 2 mmol) in DMSO (10 mL) were added KF (0.116 g, 2 mmol), potassium carbonate (0.276 g, 2 mmol) and copper acetate (0.199 g, 1 mmol) successively at room temperature. Then the mixture was heated at 150 C. for 4 h. The reaction was cooled and poured into water (20 mL) then extracted with ethyl acetate (60 mL). The organic phase was dried over anhydrous sodium sulphate. The solvent was evaporated and the residue was filtered through a plug of silica gel. The filter cake was washed with ethyl acetate/petroleum ether (1:10, v/v) and the combined filtrates concentrated to give crude 6-(2-methylpyrrolidin-1-yl)pyridin-2-amine (0.225 g, 64%) as a colourless oil. This was used directly without further purification. LC/MS: 178.1 [M+H]+.
With potassium fluoride; copper (I) acetate; potassium carbonate; In dimethyl sulfoxide; at 150℃; for 4h; To a stirred solution of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (0.224 g, 1 mmol) and 2- methylpyrrolidine (0.173 g, 2 mmol) in DMSO (10 mL) were added KF (0.116 g, 2 mmol), potassium carbonate (0.276 g, 2 mmol) and copper acetate (0.199 g, 1 mmol) successively at room temperature. Then the mixture was heated at 150C for 4 h. The reaction was cooled and poured into water (20 mL) then extracted with ethyl acetate (60 mL). The organic phase was dried over anhydrous sodium sulphate. The solvent was evaporated and the residue was filtered through a plug of silica gel. The filter cake was washed with ethyl acetate / petroleum ether (1: 10, v/v) and the combined filtrates concentrated to give crude 6-(2-methylpyrrolidin-l-yl)pyridin-2-amine (0.225 g, 64 %) as a colourless oil. This was used directly without further purification. LC/MS: 178.1[M+H]+
  • 26
  • [ 1597-32-6 ]
  • [ 3000-79-1 ]
  • [ 1314354-81-8 ]
YieldReaction ConditionsOperation in experiment
49% In water; at 205℃; for 0.5h;Microwave irradiation; A suspension of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (448 mg, 4 mmol) and 2-methylpiperidine (596 mg, 6 mmol) in water (0.5 mL) was heated to 205 C. in a microwave oven for 30 minutes. The reaction mixture was purified by chromatography (silica gel, 200-300 mesh, petroleum ether:ethyl acetate=10:1) to give 6-(2-methylpiperidin-1-yl)pyridin-2-amine (376 mg, 49%) as a brown oil. LC-MS: [M+H]+, 192.2, tR=1.266 min.
49% In water; at 205℃; for 0.5h;Microwave irradiation; A suspension of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (448 mg, 4 mmol) and 2-methylpiperidine (596 mg, 6 mmol) in water (0.5 mL) was heated to 205 C in a microwave oven for 30 minutes. The reaction mixture was purified by chromatography (silica gel, 200 - 300 mesh, petroleum ether : ethyl acetate = 10 : 1) to give 6-(2-methylpiperidin-l-yl)pyridin-2-amine (376 mg, 49 %) as a brown oil. LC-MS: [M+H]+, 192.2, tR = 1.266min.
  • 27
  • [ 1597-32-6 ]
  • (R)-(-)-2-methylpyrrolidine [ No CAS ]
  • [ 1431773-78-2 ]
YieldReaction ConditionsOperation in experiment
82% In water; at 205℃; for 0.5h;Microwave irradiation; A suspension of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (448 mg, 4 mmol) and (7^-2-methylpyrrolidine (51 1 mg, 6 mmol) in water (0.5 mL) was heated to 205 C in a microwave oven for 30 minutes. The reaction mixture was purified by chromatography (silica gel, 200 - 300 mesh, petroleum ether : ethyl acetate = 3 : 1) to give (7?y)-6-(2-methylpyrrolidin-l-yl)pyridin-2-amine (581 mg, 82 %) as light yellow oil. LC-MS : [M+H]+, 178.2, tR = 1.049min.
  • 28
  • [ 1597-32-6 ]
  • 3-Azabicyclo<3.1.0>hexane hydrochloride [ No CAS ]
  • [ 1431773-80-6 ]
YieldReaction ConditionsOperation in experiment
76% With triethylamine; In water; at 205℃; for 0.5h;Microwave irradiation; A suspension of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (448 mg, 4 mmol), 3-aza-bicyclo[3.1.0]hexane hydrochloride (576 mg, 4.8 mmol) and Et3N (808 mg, 8 mmol) in water (0.5 mL) was heated to 205 C. in a microwave oven for 30 minutes. The reaction mixture was purified by chromatography (silica gel, 200-300 mesh, petroleum ether:ethyl acetate=10:1) to give 6-(3-aza-bicyclo[3.1.0]hexan-3-yl)pyridin-2-amine (535 mg, 76%) as a colorless oil. LC-MS: [M+H]+, 176.2, tR=1.042 min.
76% With triethylamine; In water; at 205℃; for 0.5h;Microwave irradiation; A suspension of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (448 mg, 4 mmol), 3-aza-bicyclo[3.1.0]hexane hydrochloride (576 mg, 4.8 mmol) and Et3N (808 mg, 8 mmol) in water (0.5 mL) was heated to 205 C in a microwave oven for 30 minutes. The reaction mixture was purified by chromatography (silica gel, 200 - 300 mesh, petroleum ether : ethyl acetate = 10 : 1) to give 6-(3- aza-bicyclo[3.1.0]hexan-3-yl)pyridin-2-amine (535 mg, 76 %) as a colorless oil. LC-MS: [M+H]+, 176.2, tR = 1.042min.
  • 29
  • [ 1597-32-6 ]
  • (S)-2-methylpyrrolidine [ No CAS ]
  • [ 1415695-32-7 ]
YieldReaction ConditionsOperation in experiment
83% In water; at 205℃; for 0.5h;Microwave irradiation; A suspension of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (1.12 g, 10 mmol) and (S)-2-methylpyrrolidine (1.03 g, 12 mmol) in water (1 mL) was heated to 205 C. in a microwave oven for 30 minutes. The reaction mixture was purified by chromatography (silica gel, 200-300 mesh, petroleum ether:ethyl acetate=5:1) to give (S)-6-(2-methylpyrrolidin-1-yl)pyridin-2-amine (1.5 g, 83%) as a colorless oil. LC-MS: [M+H]+, 178.2, tR=1.066 min.
29% In water; at 205℃; for 0.5h;Microwave irradiation; A suspension of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (1.12 g, 10 mmol) and (5)-2-methylpyrrolidine (1.03 g, 12 mmol) in water (1 mL) was heated to 205 C in a microwave oven for 30 minutes. The reaction mixture was purified by chromatography (silica gel, 200 - 300 mesh, petroleum ether : ethyl acetate = 5 : 1) to give (S)-6-(2-methylpyrrolidin-l-yl)pyridin-2-amine (1.5 g, 83 %) as a colorless oil. LC-MS: [M+H]+, 178.2, tR = 1.066min.
  • 30
  • [ 3378-71-0 ]
  • [ 1597-32-6 ]
  • [ 1431773-87-3 ]
YieldReaction ConditionsOperation in experiment
45% In water; at 205℃; for 0.5h;Microwave irradiation; A mixture of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (0.5 g, 4.46 mmol) and 2,5-dimethylpyrrolidine (0.664 g, 6.7 mmol) in water (0.3 mL) was heated to 205 C. for 0.5 h in a microwave oven then concentrated in vacuo. The residue was purified by chromatography (silica gel, 10 g, 200˜300 mesh, ethyl acetate:petroleum ether=1:30) to afford 6-(2,5-dimethylpyrrolidin-1-yl)pyridin-2-amine (0.383 g, 45%) as a yellow oil. LC-MS: [M+1]+=192, tR=1.048 min.
45% In water; at 205℃; for 0.5h;Microwave irradiation; A mixture of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (0.5 g, 4.46 mmol) and 2,5-dimethylpyrrolidine (0.664 g, 6.7 mmol) in water (0.3 mL) was heated to 205 C for 0.5 h in a microwave oven then concentrated in vacuo. The residue was purified by chromatography (silica gel, 10 g, 200 ~ 300 mesh, ethyl acetate : petroleum ether = 1 : 30) to afford 6-(2,5-dimethylpyrrolidin-l-yl)pyridin- 2-amine (0.383 g, 45 %) as a yellow oil. LC-MS: [M + l]+ = 192 > tR = 1.048 min.
  • 31
  • [ 1003-28-7 ]
  • [ 1597-32-6 ]
  • [ 1431773-88-4 ]
YieldReaction ConditionsOperation in experiment
67% In water; at 205℃; for 0.5h;Microwave irradiation; A mixture of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (0.5 g, 4.46 mmol) and 2-ethylpyrrolidine (0.664 g, 6.7 mmol) in water (0.3 mL) was heated to 205 C. for 0.5 h in a microwave oven then concentrated in vacuo. The residue was purified by chromatography (silica gel, 10 g, 200˜300 mesh, ethyl acetate:petroleum ether=1:30) to afford 6-(2-ethylpyrrolidin-1-yl)pyridin-2-amine (0.57 g, 67%) as a yellow oil. LC-MS: [M+1]+=192, tR=1.100 min.
67% In water; at 205℃; for 0.5h;Microwave irradiation; A mixture of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (0.5 g, 4.46 mmol) and 2-ethylpyrrolidine (0.664 g, 6.7 mmol) in water (0.3 mL) was heated to 205 C for 0.5 h in a microwave oven then concentrated in vacuo. The residue was purified by chromatography (silica gel, 10 g, 200 ~ 300 mesh, ethyl acetate : petroleum ether = 1 : 30) to afford 6-(2-ethylpyrrolidin-l-yl)pyridin-2-amine (0.57 g, 67 %) as a yellow oil. LC-MS: [M + l]+ = 192 > tR = l . lOOmin.
  • 32
  • [ 792915-20-9 ]
  • [ 1597-32-6 ]
  • [ 1431773-90-8 ]
YieldReaction ConditionsOperation in experiment
78% With triethylamine; In water; at 205℃; for 0.5h;Sealed tube; Microwave irradiation; A mixture of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (0.5 g, 4.46 mmol), 3,3-dimethylpyrrolidine hydrochloride (0.73 g, 5.35 mmol) and Et3N (1.08 g, 10.7 mmol) in water (0.2 mL) was heated to 205 C. for 0.5 h in a sealed tube in a microwave oven then concentrated in vacuo. The residue was purified by chromatography (silica gel, 10 g, 200-300 mesh, ethyl acetate:petroleum ether=1:15) to afford 6-(3,3-dimethylpyrrolidin-1-yl)pyridin-2-amine (0.67 g, 78%) as a yellow oil. LC-MS: [M+1]+=192, tR=1.187 min.
78% In water; at 205℃; for 0.5h;Microwave irradiation; Sealed tube; A mixture of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (0.5g, 4.46 mmol) ' 3,3-dimethylpyrrolidine hydrochloride (0.73 g, 5.35 mmol) and Et3N (1.08 g, 10.7mmol) in water (0.2 mL) was heated to 205 C for 0.5 h in a sealed tube in a microwave oven then concentrated in vacuo. The residue was purified by chromatography (silica gel, 10 g, 200-300 mesh, ethyl acetate : petroleum ether = 1 : 15 ) to afford 6-(3,3-dimethylpyrrolidin-l-yl)pyridin-2-amine (0.67 g, 78 %) as a yellow oil. LC-MS: [M + l]+ = 192 > tR = 1.187min.
  • 33
  • [ 1597-32-6 ]
  • [ 76946-27-5 ]
  • [ 1431773-91-9 ]
YieldReaction ConditionsOperation in experiment
74% In water; at 205℃; for 0.5h;Sealed tube; Microwave irradiation; A mixture of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (0.5 g, 4.46 mmol) and 2-(methoxymethyl)pyrrolidine (0.617 g, 5.35 mmol) in water (0.2 mL) was heated to 205 C. for 0.5 h in a sealed tube in a microwave oven then concentrated in vacuo. The residue was purified by chromatography (silica gel, 10 g, 200˜300 mesh, ethyl acetate:petroleum ether=1:15) to afford 6-(2-(methoxymethyl)pyrrolidin-1-yl)pyridin-2-amine (0.68 g, 74%) as a yellow oil. LC-MS: [M+1]+=208, tR=1.052 min.
74% In water; at 205℃; for 0.5h;Microwave irradiation; Sealed tube; A mixture of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (0.5 g, 4.46 mmol) and 2-(methoxymethyl)pyrrolidine (0.617 g, 5.35 mmol) in water (0.2 mL) was heated to 205 C for 0.5 h in a sealed tube in a microwave oven then concentrated in vacuo. The residue was purified by chromatography (silica gel, 10 g, 200 ~ 300 mesh, ethyl acetate : petroleum ether = 1 : 15 ) to afford 6-(2- (methoxymethyl)pyrrolidin-l-yl)pyridin-2-amine (0.68 g, 74 %) as a yellow oil. LC-MS: [M + l]+ =208 ' tR = 1.052min.
  • 34
  • [ 35794-11-7 ]
  • [ 1597-32-6 ]
  • [ 1431773-93-1 ]
YieldReaction ConditionsOperation in experiment
83% In water; at 205℃; for 0.5h;Sealed tube; Microwave irradiation; A mixture of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (0.5 g, 4.46 mmol) and 3,5-dimethylpiperidine (0.61 g, 5.35 mmol) in water (0.2 mL) was heated to 205 C. for 0.5 h in a sealed tube in a microwave oven then concentrated in vacuo. The residue was purified by chromatography (silica gel, 10 g, 200-300 mesh, ethyl acetate:petroleum ether=1:8) to afford 6-(3,5-dimethylpiperidin-1-yl)pyridin-2-amine (0.76 g, 83%) as a yellow oil. LC-MS: [M+1]+=206, tR=1.240 min.
83% In water; at 205℃; for 0.5h;Microwave irradiation; Sealed tube; A mixture of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (0.5 g, 4.46 mmol) and 3,5-dimethylpiperidine (0.61 g, 5.35 mmol) in water (0.2 mL) was heated to 205 C for 0.5 h in a sealed tube in a microwave oven then concentrated in vacuo. The residue was purified by chromatography (silica gel, 10 g, 200-300 mesh, ethyl acetate : petroleum ether = 1 : 8 ) to afford 6-(3,5-dimethylpiperidin-l- yl)pyridin-2-amine (0.76 g, 83 %) as a yellow oil. LC-MS: [M + l]+ = 206 > tR = 1.240min.
  • 35
  • [ 35018-15-6 ]
  • [ 1597-32-6 ]
  • [ 1431773-89-5 ]
YieldReaction ConditionsOperation in experiment
4% In water; at 205℃; for 0.5h;Sealed tube; Microwave irradiation; A mixture of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (0.5 g, 4.46 mmol) and 2,2-dimethylpyrrolidine (0.67 g, 6.75 mmol) in water (0.3 mL) was heated to 205 C. for 0.5 h in a sealed tube in a microwave oven then concentrated in vacuo. The residue was purified by chromatography (silica gel, 10 g, 200˜300 mesh, ethyl acetate:petroleum ether=1:15) to afford 6-(2,2-dimethylpyrrolidin-1-yl)pyridin-2-amine (0.035 g, 4%) as a yellow oil. LC-MS: [M+1]+=192, tR=1.048 min.
4% In water; at 205℃; for 0.5h;Microwave irradiation; Sealed tube; A mixture of <strong>[1597-32-6]6-fluoropyridin-2-amine</strong> (0.5 g, 4.46 mmol) and 2,2-dimethylpyrrolidine (0.67 g, 6.75 mmol) in water (0.3 mL) was heated to 205 C for 0.5 h in a sealed tube in a microwave oven then concentrated in vacuo. The residue was purified by chromatography (silica gel, 10 g, 200 ~ 300 mesh, ethyl acetate : petroleum ether = 1 : 15 ) to afford 6-(2,2-dimethylpyrrolidin-l- yl) pyridin-2-amine (0.035 g, 4 %) as a yellow oil. LC-MS: [M + l]+ = 192 > tR = 1.048min.
 

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