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Structure of 877399-49-0

Chemical Structure| 877399-49-0

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Product Details of [ 877399-49-0 ]

CAS No. :877399-49-0
Formula : C19H22BCl2FN2O3
M.W : 427.11
SMILES Code : NC1=NC=C(B2OC(C)(C)C(C)(C)O2)C=C1O[C@@H](C3=C(Cl)C=CC(F)=C3Cl)C
MDL No. :MFCD22495029

Safety of [ 877399-49-0 ]

Application In Synthesis of [ 877399-49-0 ]

* 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 [ 877399-49-0 ]

[ 877399-49-0 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 877399-50-3 ]
  • [ 877399-49-0 ]
  • 4-(4-{6-amino-5-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% With nitrogen; sodium carbonate;Pd(PPh3)2Cl2; In 1,2-dimethoxyethane; water; ethyl acetate; To a stirred solution of 3-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine (15.22 g, 35.64 mmol) and <strong>[877399-50-3]4-(4-bromo-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester</strong> (14.12 g, 42.77 mmol) in DME (143 mL) was added a solution of Na2CO3 (11.33 g, 10692 mmol) in water (36 mL). The solution was degassed and charged with nitrogen three times. To the solution was added Pd(PPh3)2Cl2 (1.25 mg, 1.782 mmol). The reaction solution was degassed and charged with nitrogen again three times. The reaction solution was stirred at 87° C. oil bath for about 16 hours (or until consumption of the borane pinacol ester), cooled to ambient temperature and diluted with EtOAc (600 mL). The reaction mixture was filtered through a pad of celite and washed with EtOAc. The EtOAc solution was washed with brine, dried over Na2SO4, and concentrated. The crude product was purified on a silica gel column eluding with EtOAc/Hexane system (Biotage 90+Column: equilibrium 600 mL 100percent Hexanes, segment 1: 2250 mL 50percent EtOAc/Hexanes Linear, segment 2: 4500 mL 75percent EtOAc/Hexanes Linear, segment 3: 4500 mL 100percent EtOAc) to afford 4-(4-{6-amino-5-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (11.8 g, 60percent yield, ~95percent purity) with a Rf of 0.15 (50percent EtOAc/Hexanes). MS m/e 550 (M+1)+.
65% With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; water; ethyl acetate; at 87℃; for 16h; To a stirred solution of 3-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine (4.2711 g, 10.0 mmol) and <strong>[877399-50-3]4-(4-bromo-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester</strong> (see procedure 11) (3.9628 g, 12.0 mmol) in DME (40 mL) was added a solution of Na2CO3 (3.1787 g, 30.0 mmol) in water (10 mL). The solution was degassed and charged with nitrogen three times. To the solution was added Pd(PPh3)2Cl2 (351 mg, 0.50 mmol). The reaction solution was degassed and charged with nitrogen again three times. The reaction solution was stirred at 87° C. oil bath for about 16 hours (or until consumption of the borane pinacol ester), cooled to ambient temperature and diluted with EtOAc (200 mL). The reaction mixture was filtered through a pad of celite and washed with EtOAc. The EtOAc solution was washed with brine, dried over Na2SO4, and concentrated. The crude product was purified on a silica gel column eluding with EtOAc/hexane system (0percent EtOAc to 100percent EtOAc) to afford 4-(4-{6-amino-5-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (3.4167 g, 65percent yield, 95percent purity) with a Rf of 0.15 (50percent EtOAc/Hexanes). MS m/e 550 (M+1)+.
65% With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; water; at 87℃; for 16h; To a stirred solution of 3-[(fl)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine (4.2711 g, 10.0 mmol) and <strong>[877399-50-3]4-(4-bromo-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester</strong> (see procedure 11) (3.9628 g, 12.0 mmol) in DME (40 mL) was added a solution of Na2CO3 (3.1787 g, 30.0 mmol) in water (10 mL). The solution was degassed and charged with nitrogen three times. To the solution was added Pd(PPh3)2CI2 (351 mg, 0.50 mmol). The reaction solution was degassed and charged with nitrogen again three times. The reaction solution was stirred at 87°C oil bath for about 16 hours (or until consumption of the borane pinacol ester), cooled to ambient temperature and diluted with EtOAc (200 mL). The reaction mixture was filtered through a pad of celite and washed with EtOAc. The EtOAc solution was washed with brine, dried over Na2SO4, and concentrated. The crude product was purified on a silica gel column eluting with EtOAc/hexane system (0percent EtOAc to 100percent EtOAc) to afford 4-(4-{6-amino-5-[(fl)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (3.4167 g, 65percent yield, -95percent purity) with a Rf of 0.15 (50percent EtOAc/Hexanes). MS m/e 550 (M+1)+.
65% With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In 1,2-dimethoxyethane; water; at 87℃; for 16h;Inert atmosphere; To a stirred solution of 3-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine (4.2711 g, 10.0 mmol) and <strong>[877399-50-3]4-(4-bromo-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester</strong> (3.9628 g, 12.0 mmol) in DME (40 mL) was added a solution of Na2CO3 (3.1787 g, 30.0 mmol) in water (10 mL). The solution was degassed and charged with nitrogen three times. To the solution was added Pd(PPh3J2CI2 (351 mg, 0.50 mmol). The reaction solution was degassed and charged with nitrogen again three times. The reaction solution was stirred at 87° C. oil bath for about 16 hours (or until consumption of the borane pinacol ester), cooled to ambient temperature and diluted with EtOAc (200 mL). The reaction mixture was filtered through a pad of celite and washed with EtOAc. The EtOAc solution was washed with brine, dried over Na2SO4, and concentrated. The crude product was purified on a silica gel column eluting with EtOAc/hexane system (0percent EtOAc to 100percent EtOAc) to afford 4-(4-{6-amino-5-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (3.4167 g, 65percent yield, ?95percent purity) with a Rf of 0.15 (50percent EtOAc/Hexanes). MS m/e 550 (M+1)+.
60% With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; water; for 16h;Heating / reflux; To a stirred solution of 3-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine (15.22 g, 35.64 mmol) and <strong>[877399-50-3]4-(4-bromo-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester</strong> (14.12 g, 42.77 mmol) in DME (143 mL) was added a solution of Na2CO3 (11.33 g, 10692 mmol) in water (36 mL). The solution was degassed and charged with nitrogen three times. To the solution was added Pd(PPh3)2Cl2 (1.25 g, 1.782 mmol). The reaction solution was degassed and charged with nitrogen again three times. The reaction solution was stirred at 87° C. oil bath for about 16 hours (or until consumption of the borane pinacol ester), cooled to ambient temperature and diluted with EtOAc (600 mL). The reaction mixture was filtered through a pad of celite and washed with EtOAc. The EtOAc solution was washed with brine, dried over Na2SO4, and concentrated. The crude product was purified on a silica gel column eluting with EtOAc/Hexane system (Biotage 90+ Column: equilibrium 600 mL 100percent Hexanes, segment 1:2250 mL 50percent EtOAc/Hexanes Linear, segment 2: 4500 mL 75percent EtOAc/Hexanes Linear, segment 3: 4500 mL 100percent EtOAc) to afford 4-(4-{6-amino-5-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (11.8 g, 60percent yield, 95percent purity) with a Rf of 0.15 (50percent EtOAc/Hexanes). MS m/e 550 (M+1)+.
60% To a stirred solution of 3-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine (15.22 g, 35.64 mmol) and <strong>[877399-50-3]4-(4-bromo-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester</strong> (14.12 g, 42.77 mmol) in DME (143 mL) was added a solution of Na2CO3 (11.33 g, 10692 mmol) in water (36 mL). The solution was degassed and charged with nitrogen three times. To the solution was added Pd(PPh3)2Cl2 (1.25 mg, 1.782 mmol). The reaction solution was degassed and charged with nitrogen again three times. The reaction solution was stirred at 87° C. oil bath for about 16 hours (or until consumption of the borane pinacol ester), cooled to ambient temperature and diluted with EtOAc (600 mL). The reaction mixture was filtered through a pad of Celite® and washed with EtOAc. The EtOAc solution was washed with brine, dried over Na2SO4, and concentrated. The crude product was purified on a silica gel column eluting with EtOAc/Hexane system (Biotage 90+ Column: equilibrium 600 mL 100percent Hexanes, segment 1: 2250 mL 50percent EtOAc/Hexanes Linear, segment 2: 4500 mL 75percent EtOAc/Hexanes Linear, segment 3: 4500 mL 100percent EtOAc) to afford 4-(4-{6-amino-5-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (11.8 g, 60percent yield, ?95percent purity) with a Rf of 0.15 (50percent EtOAc/Hexanes). MS m/e 550 (M+1)+.

  • 2
  • [ 877399-50-3 ]
  • [ 877399-49-0 ]
  • crizotinib [ No CAS ]
  • 3
  • [ 877399-49-0 ]
  • [ 832735-58-7 ]
  • (R)-6-amino-1'-ethyl-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-[3,4'-bipyridine]-2'(1'H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; caesium carbonate; In 1,4-dioxane; water; at 110℃; for 10h;Inert atmosphere; General procedure: To a 50mL round-bottom flask under a nitrogen atmosphere 7 (10.0 mmol), bispinacolatodiboron (10.0 mmol), PdCl2(dppf)2 (0.5 mmol), potassium acetate (15 mmol) and 1, 4-dioxane (20 mL) were added. The reaction mixture was stirred at 80 C for 8 h. After the completion of the reaction, Cs2CO3 (15 mmol), PdCl2(dppf)2 (0.5 mmol), 3 (11.0 mmol) and 0.5 mL H2O were added to the above mixture. The reaction was stirred at 110 C overnight. After the completion of the reaction, 20 mL of H2O was added and the reaction mixture was extracted with DCM for 3 times. The combined organic layer was collected and rinsed with brine. The mixture was evaporated to obtain the crude product and purified by silica gel for 8a-8l.
 

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