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[ CAS No. 42718-13-8 ] {[proInfo.proName]}

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Chemical Structure| 42718-13-8
Chemical Structure| 42718-13-8
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Product Details of [ 42718-13-8 ]

CAS No. :42718-13-8 MDL No. :MFCD12149120
Formula : C9H10FNO2 Boiling Point : -
Linear Structure Formula :- InChI Key :MWURXQVPORPSQD-UHFFFAOYSA-N
M.W : 183.18 Pubchem ID :10943118
Synonyms :

Safety of [ 42718-13-8 ]

Signal Word:Danger Class:8
Precautionary Statements:P261-P264-P271-P280-P302+P352-P304+P340+P312-P305+P351+P338+P310-P332+P313-P362-P403+P233-P405-P501 UN#:3259
Hazard Statements:H315-H318-H335 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 42718-13-8 ]

* 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 [ 42718-13-8 ]

[ 42718-13-8 ] Synthesis Path-Downstream   1~50

  • 2
  • [ 135822-91-2 ]
  • [ 42718-13-8 ]
  • [ 403-43-0 ]
  • 3-[2,5-bis-(4-fluoro-phenyl)-1<i>H</i>-imidazol-4-yl]-pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
49% Multistep reaction;
  • 3
  • [ 42718-13-8 ]
  • [ 403-43-0 ]
  • [ 208641-14-9 ]
  • 4-[2,5-bis-(4-fluoro-phenyl)-1<i>H</i>-imidazol-4-yl]-pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% Multistep reaction;
  • 4
  • [ 135822-91-2 ]
  • [ 42718-13-8 ]
  • [ 98-88-4 ]
  • 3-[5-(4-fluoro-phenyl)-2-phenyl-1<i>H</i>-imidazol-4-yl]-pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
53% Multistep reaction;
  • 5
  • [ 42718-13-8 ]
  • [ 98-88-4 ]
  • [ 208641-14-9 ]
  • 4-[5-(4-fluorophenyl)-2-phenyl-1H-imidazol-4-yl]pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% Multistep reaction;
  • 6
  • [ 135822-91-2 ]
  • [ 42718-13-8 ]
  • [ 100-07-2 ]
  • 3-[5-(4-fluoro-phenyl)-2-(4-methoxy-phenyl)-1<i>H</i>-imidazol-4-yl]-pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
66% Multistep reaction;
  • 7
  • [ 42718-13-8 ]
  • [ 100-07-2 ]
  • [ 208641-14-9 ]
  • [ 152121-61-4 ]
YieldReaction ConditionsOperation in experiment
89% Multistep reaction;
  • 8
  • [ 42718-13-8 ]
  • [ 19883-57-9 ]
YieldReaction ConditionsOperation in experiment
11 α-Amino-4-fluorobenzeneacetic acid methyl ester EXAMPLE 11 α-Amino-4-fluorobenzeneacetic acid methyl ester 4-Fluoro-α-[(phenylmethyl)amino]benzeneacetic acid methyl ester hydrochloride (12.2 kg, 39.4 moles) was added to a slurry of 10% palladium-on-carbon (1.2 kg) in isopropanol (50 L). Ammonium formate (5.0 kg, 79.4 moles) was added and the batch was heated to 50° C. Progress of the reaction was monitored by HPLC. The batch was filtered through Hyflo Supercel and the filter cake was washed with isopropanol (25 L). The filtrate was evaporated to low volume and flushed with isopropyl acetate (50 L). The residue was dissolved in isopropyl acetate (30 L) and washed with 5% aqueous potassium phosphate (40 L), followed by saturated aqueous sodium chloride (10 L).
12 (S)-α-Amino-4-fluorobenzeneacetic acid EXAMPLE 12 (S)-α-Amino-4-fluorobenzeneacetic acid A solution of racemic α-amino-4-fluorobenzeneacetic acid methyl ester (3.32 kg, 18.2 moles) in 96% ethanol (5 L) was filtered then water (500 mL) was added to it. A solution of di-O-benzoyl-D-tartaric acid (DBT, 1.32 kg, 3.7 moles) in water:ethanol (1:7, 2.86 L) was then added. The crystallization mixture was cooled to 5° C. and aged for 1.5 hours. The product was collected by filtration, washed with water:ethanol (1:7, 1.1 L), air dried, then dried under vacuum at 50° C. to give 1.91 kg of α-amino-4-fluorobenzeneacetic acid methyl ester, DBT salt (95.8% ee). Solvent (6.6 L) was removed from the liquors by evaporation under reduced pressure.
101 (S)-α-Amino-4-fluorobenzeneacetic acid EXAMPLE 101 (S)-α-Amino-4-fluorobenzeneacetic acid A solution of racemic α-amino-4-fluorobenzeneacetic acid methyl ester (3.32 kg, 18.2 moles) in 96% ethanol (5 L) was filtered then water (500 mL) was added to it. A solution of di-O-benzoyl-D-tartaric acid (DBT, 1.32 kg, 3.7 moles) in water:ethanol (1:7, 2.86 L) was then added. The crystallization mixture was cooled to 5° C. and aged for 1.5 hours. The product was collected by filtration, washed with water:ethanol (1:7, 1.1 L), air dried, then dried under vacuum at 50° C. to give 1.91 kg of α-amino-4-fluorobenzeneacetic acid methyl ester, DBT salt (95.8% ee). Solvent (6.6 L) was removed from the liquors by evaporation under reduced pressure.
97 (S)-α-Amino-4-fluorobenzeneacetic acid EXAMPLE 97 (S)-α-Amino-4-fluorobenzeneacetic acid A solution of racemic α-amino-4-fluorobenzeneacetic acid methyl ester (3.32 kg, 18.2 moles) in 96% ethanol (5 L) was filtered then water (500 mL) was added to it. A solution of di-O-benzoyl-D-tartaric acid (DBT, 1.32 kg, 3.7 moles) in water:ethanol (1:7, 2.86 L) was then added. The crystallization mixture was cooled to 5° C. and aged for 1.5 hours. The product was collected by filtration, washed with water:ethanol (1:7, 1.1 L), air dried, then dried under vacuum at 50° C. to give 1.91 kg of α-amino-4-fluorobenzeneacetic acid methyl ester, DBT salt (95.8% ee). Solvent (6.6 L) was removed from the liquors by evaporation under reduced pressure.

YieldReaction ConditionsOperation in experiment
87% 100 α-Amino-4-fluorobenzeneacetic acid methyl ester EXAMPLE 100 α-Amino-4-fluorobenzeneacetic acid methyl ester 4-Fluoro-α-[(phenylmethyl)amino]benzeneacetic acid methyl ester hydrochloride (12.2 kg, 39.4 moles) was added to a slurry of 10% palladium-on-carbon (1.2 kg) in isopropanol (50 L). Ammonium formate (5.0 kg, 79.4 moles) was added and the batch was heated to 50° C. Progress of the reaction was monitored by HPLC. The batch was filtered through Hyflo Supercel and the filter cake was washed with isopropanol (25 L). The filtrate was evaporated to low volume and flushed with isopropyl acetate (50 L). The residue was dissolved in isopropyl acetate (30 L) and washed with 5% aqueous potassium phosphate (40 L), followed by saturated aqueous sodium chloride (10 L). The solution was evaporated under vacuum to give 5.79 kg (87% yield) of racemic α-amino-4-fluorobenzeneacetic acid methyl ester.
87% 96 α-Amino-4-fluorobenzeneacetic acid methyl ester EXAMPLE 96 α-Amino-4-fluorobenzeneacetic acid methyl ester 4-Fluoro-α-[(phenylmethyl)amino]benzeneacetic acid methyl ester hydrochloride (12.2 kg, 39.4 moles) was added to a slurry of 10% palladium-on-carbon (1.2 kg) in isopropanol (50 L). Ammonium formate (5.0 kg, 79.4 moles) was added and the batch was heated to 50° C. Progress of the reaction was monitored by HPLC. The batch was filtered through Hyflo Supercel and the filter cake was washed with isopropanol (25 L). The filtrate was evaporated to low volume and flushed with isopropyl acetate (50 L). The residue was dissolved in isopropyl acetate (30 L) and washed with 5% aqueous potassium phosphate (40 L), followed by saturated aqueous sodium chloride (10 L). The solution was evaporated under vacuum to give 5.79 kg (87% yield) of racemic α-amino-4-fluorobenzeneacetic acid methyl ester.
  • 11
  • [ 42718-13-8 ]
  • [ 7693-46-1 ]
  • [ 902133-70-4 ]
YieldReaction ConditionsOperation in experiment
Stage #1: 4-amino-1-benzylpiperidine; 4-Nitrophenyl chloroformate With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0℃; for 1h; Stage #2: α-amino-4-fluorobenzeneacetic acid methyl ester In tetrahydrofuran at 20℃; 4-Amino-l-benzylpiperidine (460 mg, 2.42 mmol) in tetrahydrofuran (15 mL) was added to a solution of p-nitrophenylchloroformate (487 mg, 2.42 mmol) and diisopropylethylamine (430 uL, 2.42 mmol) in tetrahydrofuran (5 mL) at 0 0C. After 1 h, additional diisopropylethylamine was added (860 uL, 4.84 mmol) along with methyl amino(4-fluorophenyl)acetate (443 mg, 2.42 mmol). The reaction was wanned to room temperature and stirred overnight. The mixture was filtered, concentrated and redissolved in ethyl acetate. The ethyl acetate layer was washed with IN sodium hydroxide (3x), saturated sodium bicarbonate solution, water, brine, and dried over sodium sulfate. The crude product was EPO purified by column chromatography (silica gel, 0 to 5%/methanol in methylene chloride gradient elution), giving the title compound (700 mg). MS 400.29 (M+ 1)
  • 12
  • [ 67-56-1 ]
  • [ 7292-73-1 ]
  • [ 42718-13-8 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; at 0 - 20℃; for 18h; HCl (g) was bubbled into a solution of 4-fluoro-DL-phenylglycine (810 mg, 4.79 mmol") in methanol (20 mL) for 5 min at 0 0C. The reaction wanned to ambient temperature and stirred for 18 h. The mixture was concentrated to give the title compound (1 g). MS 183.9 (M+ 1)
With sulfuric acid;Reflux; General procedure: The amino acid (1.0 mmol, 1.0 eq) was dispersed in MeOH (1.0 mL per 0.21 mmol of amino acid) with concd H2SO4 (1.8 eq). The mixture was refluxed overnight, at which point LC-MS analysis indicated complete conversion had taken place. The mixture was cooled then concentrated under reduced pressure. The resulting residue was basified with sat. NaHCO3(aq), then extracted with DCM. The combined organic layers were concentrated under reduced pressure. This was taken up into water and THF (5:1), before adding in Boc2O (1.05 eq), and stirring at room temperature overnight. The mixture was diluted with water, before extraction with DCM. Concentration of the combined organic layers gave the desired product.
  • 13
  • 1-acetyl-3-(2-fluorobenzylidene)indolinone [ No CAS ]
  • [ 42718-13-8 ]
  • [ 555-16-8 ]
  • [ 1190309-10-4 ]
  • diethyl 1-acetyl-4'-(2-fluorophenyl)-5'-(4-nitrophenyl)-2-oxospiro[indoline-3,3'-pyrrolidine]-2',2'-dicarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With (R)-2,6-bis(naphthalen-2-yl)-4-oxo-3,5-dioxa-4λ5-phosphacyclohepta[2,1-a;3,4-a']dinapthalen-4-ol In dichloromethane at 25℃; Molecular sieve; optical yield given as %ee; enantioselective reaction;
  • 14
  • 1-acetyl-3-(2-chlorobenzylidene)indolinone [ No CAS ]
  • [ 42718-13-8 ]
  • [ 555-16-8 ]
  • [ 1190309-11-5 ]
  • diethyl 1-acetyl-4'-(2-chlorophenyl)-5'-(4-nitrophenyl)-2-oxospiro[indoline-3,3'-pyrrolidine]-2',2'-dicarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With (R)-2,6-bis(naphthalen-2-yl)-4-oxo-3,5-dioxa-4λ5-phosphacyclohepta[2,1-a;3,4-a']dinapthalen-4-ol In dichloromethane at 25℃; Molecular sieve; optical yield given as %ee; enantioselective reaction;
  • 15
  • C17H12ClNO2 [ No CAS ]
  • [ 42718-13-8 ]
  • [ 555-16-8 ]
  • [ 1190309-12-6 ]
YieldReaction ConditionsOperation in experiment
93% With (R)-2,6-bis(naphthalen-2-yl)-4-oxo-3,5-dioxa-4λ5-phosphacyclohepta[2,1-a;3,4-a']dinapthalen-4-ol In dichloromethane at 25℃; Molecular sieve; optical yield given as %ee; enantioselective reaction;
  • 16
  • C17H11Cl2NO2 [ No CAS ]
  • [ 42718-13-8 ]
  • [ 555-16-8 ]
  • [ 1190309-13-7 ]
YieldReaction ConditionsOperation in experiment
91% With (R)-2,6-bis(naphthalen-2-yl)-4-oxo-3,5-dioxa-4λ5-phosphacyclohepta[2,1-a;3,4-a']dinapthalen-4-ol In dichloromethane at 25℃; Molecular sieve; optical yield given as %ee; enantioselective reaction;
  • 17
  • C21H15NO2 [ No CAS ]
  • [ 42718-13-8 ]
  • [ 555-16-8 ]
  • [ 1190309-14-8 ]
YieldReaction ConditionsOperation in experiment
90% With (R)-2,6-bis(naphthalen-2-yl)-4-oxo-3,5-dioxa-4λ5-phosphacyclohepta[2,1-a;3,4-a']dinapthalen-4-ol In dichloromethane at 25℃; Molecular sieve; optical yield given as %ee; enantioselective reaction;
  • 18
  • [ 1048976-34-6 ]
  • [ 42718-13-8 ]
  • [ 555-16-8 ]
  • [ 1190309-15-9 ]
YieldReaction ConditionsOperation in experiment
92% With (R)-2,6-bis(naphthalen-2-yl)-4-oxo-3,5-dioxa-4λ5-phosphacyclohepta[2,1-a;3,4-a']dinapthalen-4-ol In dichloromethane at 25℃; Molecular sieve; optical yield given as %ee; enantioselective reaction;
  • 19
  • [ 64259-17-2 ]
  • [ 42718-13-8 ]
  • [ 555-16-8 ]
  • [ 1190309-16-0 ]
YieldReaction ConditionsOperation in experiment
74% With (R)-2,6-bis(naphthalen-2-yl)-4-oxo-3,5-dioxa-4λ5-phosphacyclohepta[2,1-a;3,4-a']dinapthalen-4-ol In dichloromethane at 25℃; Molecular sieve; optical yield given as %ee; enantioselective reaction;
  • 20
  • 1-acetyl-3-((E)-3-phenylallylidene)indolinone [ No CAS ]
  • [ 42718-13-8 ]
  • [ 555-16-8 ]
  • C33H31N3O8 [ No CAS ]
  • [ 1190309-17-1 ]
YieldReaction ConditionsOperation in experiment
With (R)-2,6-bis(naphthalen-2-yl)-4-oxo-3,5-dioxa-4λ5-phosphacyclohepta[2,1-a;3,4-a']dinapthalen-4-ol In dichloromethane at 25℃; Molecular sieve; optical yield given as %ee; enantioselective reaction;
  • 21
  • C15H17NO2 [ No CAS ]
  • [ 42718-13-8 ]
  • [ 555-16-8 ]
  • C29H33N3O8 [ No CAS ]
  • [ 1190309-18-2 ]
  • diethyl 1-acetyl-4'-isobutyl-5'-(4-nitrophenyl)-2-oxospiro[indoline-3,3'-pyrrolidine]-2',2'-dicarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With (R)-2,6-bis(naphthalen-2-yl)-4-oxo-3,5-dioxa-4λ5-phosphacyclohepta[2,1-a;3,4-a']dinapthalen-4-ol In dichloromethane at 25℃; Molecular sieve; optical yield given as %ee; enantioselective reaction;
  • 22
  • C14H15NO2 [ No CAS ]
  • [ 42718-13-8 ]
  • [ 555-16-8 ]
  • C28H31N3O8 [ No CAS ]
  • [ 1190309-19-3 ]
  • diethyl 1-acetyl-5'-(4-nitrophenyl)-2-oxo-4'-propylspiro[indoline-3,3'-pyrrolidine]-2',2'-dicarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With (R)-2,6-bis(naphthalen-2-yl)-4-oxo-3,5-dioxa-4λ5-phosphacyclohepta[2,1-a;3,4-a']dinapthalen-4-ol In dichloromethane at 25℃; Molecular sieve; optical yield given as %ee; enantioselective reaction;
  • 23
  • [ 22144-87-2 ]
  • [ 42718-13-8 ]
  • [ 555-16-8 ]
  • [ 1190308-85-0 ]
  • methyl 1-acetyl-2'-(4-fluorophenyl)-5'-(4-nitrophenyl)-2-oxo-4'-phenylspiro[indoline-3,3'-pyrrolidine]-2'-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With (R)-2,6-bis(naphthalen-2-yl)-4-oxo-3,5-dioxa-4λ5-phosphacyclohepta[2,1-a;3,4-a']dinapthalen-4-ol In dichloromethane at 25℃; Molecular sieve; optical yield given as %ee; enantioselective reaction;
  • 24
  • [ 42718-13-8 ]
  • [ 83611-34-1 ]
  • [ 1227294-09-8 ]
YieldReaction ConditionsOperation in experiment
84% With (R)-2,6-bis(naphthalen-2-yl)-4-oxo-3,5-dioxa-4λ5-phosphacyclohepta[2,1-a;3,4-a']dinapthalen-4-ol In toluene at 25℃; for 72h; Molecular sieve; optical yield given as %ee; enantioselective reaction;
  • 25
  • [ 42718-13-8 ]
  • [ 555-16-8 ]
  • [ 624-48-6 ]
  • [ 1322877-81-5 ]
YieldReaction ConditionsOperation in experiment
94% With C42H28O9P2 In chloroform at 50℃; for 60h; Molecular sieve; optical yield given as %ee; enantioselective reaction;
  • 26
  • [ 42718-13-8 ]
  • monensin A [ No CAS ]
  • C45H70FNO12 [ No CAS ]
YieldReaction ConditionsOperation in experiment
94% Stage #1: monensin A With benzotriazol-1-ol In tetrahydrofuran at 5℃; for 0.5h; Stage #2: With dicyclohexyl-carbodiimide In tetrahydrofuran for 1h; Stage #3: α-amino-4-fluorobenzeneacetic acid methyl ester In tetrahydrofuran at 20℃; for 96h; 2 Compound (4c)-Methyl 2'-(monensinamido)-2'-(4'-fluorophenyl)acetate; NMR 1H (400 MHz, CDCl3) ppm: 8.62-8.58 (1H, m), 7.40-7.31 (2H, m), 7.08-7.00 (2H, td, J1=2.24 Hz, J2=8.8 Hz), 5.55 (1H, dd, J1=7.56 Hz, J2=43.80 Hz), 4.31-4.26 (1H, m), 4.18-4.10 (1H, m), 3.92 (1H, d, J=4.52 Hz), 3.89-3.75 (2H, m), 3.70 (3H, s), 3.69-3.49 (2H, m), 3.45-3.37 (4H, m), 3.29 (1H, m), 2.60-2.57 (1H, m), 2.27-2.20 (1H, m), 2.18-1.62 (12H, m), 1.55-1.30 (8H, m), 1.28-1.18 (3H, m), 1.03-0.73 (21H, m).NMR 13C (400 MHz, CDCl3) ppm: 175.05, 171.18, 163.66, 161.25, 129.66 (t, J=8 Hz), 116.15 (dd, J1=4 Hz, J2=22 Hz), 107.58, 97.39, 86.83, 86.32, 85.81, 83.62, 82.59, 76.86, 75.88, 71.69, 68.23, 67.56, 59.20, 58.80, 56.03 (d, J=65.2 Hz), 42.91, 39.40, 37.35, 37.23, 37.00, 35.23, 34.92, 33.75, 33.13, 33.09, 31.33, 30.27, 28.08, 26.30, 17.72, 16.72, 15.96, 14.28, 13.08, 11.46, 11.23, 8.60.Exact mass: HR ESIMS: Calculated for C45H70O12NFNa+=858.4780, found=858.4781.; A mixture of monensin acid (370 mg, 0.55 mmol, 1 eq) and HOBt (89.9 mg, 0.66 mmol, 1.2 eq) in THF (3.7 mL) was stirred at 5° C. for 30 min and then DCC (136.8 mg, 0.66 mmol, 1.2 eq) was added. After being stirred for 1 h, the reaction mixture was treated with 4-Fluoro-DL-alpha-phenylglycine methanoate (133.1 mg, 0.72 mmol, 1.3 eq) and stirring was maintained at room temperature during 4 days. The mixture was evaporated to dryness to give a powder, which was suspended in EtOAc (6 mL) and filtered off. The organic phase was washed with 10% citric acid solution (3 mL), saturated NaHCO3 (3 mL) and distilled water (3 mL), successively, dried over MgSO4 and evaporated to dryness to afford 433.9 mg (94%) of the desired amide.
  • 27
  • [ 42718-13-8 ]
  • [ 555-16-8 ]
  • [ 3623-15-2 ]
  • [ 1325732-16-8 ]
  • [ 1325732-18-0 ]
  • methyl 4-benzoyl-2-(4-fluorophenyl)-5-(4-nitrophenyl)-2,5-dihydro-1H-pyrrole-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 89 % ee 2: 97 % ee Stage #1: α-amino-4-fluorobenzeneacetic acid methyl ester; 4-nitrobenzaldehdye With (R)-3,3'-bis(9-anthracenyl)-1,1'-binaphthyl-2,2'-diyl hydrogenphosphate In toluene at 25℃; for 0.333333h; Molecular sieve; Stage #2: phenyl propargyl ketone In toluene at 25℃; for 60h; Molecular sieve; Overall yield = 79 %; enantioselective reaction;
  • 28
  • [ 1415501-19-7 ]
  • [ 42718-13-8 ]
  • [ 1609081-88-0 ]
YieldReaction ConditionsOperation in experiment
84% With 4-methyl-morpholine; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate In N,N-dimethyl-formamide at 20℃; Inert atmosphere; 1 Example 1 rac-Methyl [({8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridin-3-yl}carbonyl)amino]-(4-fluorophenyl)acetate Example 1 rac-Methyl [({8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridin-3-yl}carbonyl)amino]-(4-fluorophenyl)acetate Under argon, 750 mg of 8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid Example 3A (2.36 mmol, 1 equivalent) were suspended in 15 ml of DMF, and 1.13 g of (benzotriazol-1-yloxy)bisdimethylaminomethylium fluoroborate (TBTU, 3.54 mmol, 1.5 equivalents), 1.3 ml of 4-methylmorpholine (1.19 g, 11.78 mmol, 5 equivalents) and 517 mg of methyl amino(4-fluorophenyl)acetate (2.83 mmol, 1.2 equivalents, prepared according to Merck and Co., Inc, Patent: U.S. Pat. No. 5,691,336A1, 1997) were added in succession. The mixture was stirred at RT overnight, and about 150 ml of water were then added. The solid obtained was filtered off, washed thoroughly with water and with a little diethyl ether and dried under reduced pressure. This gave 990 mg (84% of theory; purity: 97%) of the title compound. LC-MS (Method 2): Rt=1.04 min MS (ESpos): m/z=484.2 (M+H)+ 1H-NMR (400 MHz, DMSO-d6): δ=3.68 (s, 3H), 5.31 (s, 2H), 5.69 (d, 1H), 6.95 (t, 1H), 7.03 (d, 1H), 7.19-7.29 (m, 4H), 7.53-7.63 (m, 3H), 8.53 (d, 1H), 8.72 (d, 1H), [further signal hidden under DMSO peak].
  • 29
  • [ 42718-13-8 ]
  • [ 120-36-5 ]
  • [ 1418283-37-0 ]
YieldReaction ConditionsOperation in experiment
99% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 16h; General procedure: To solutions of <strong>[120-36-5]2-(2,4-dichlorophenoxy)propanoic acid</strong>(100 mg, 0.43 mmol) in DMF (2 mL) were added 2-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate(HATU; 200 mg, 0.53 mmol), the correspondingbenzylamines (0.50 mmol), and diisopropylethylamine (100 lL,0.57 mmol). The resulting mixtures were stirred at room temperaturefor 16 h, then poured into water (20 mL). The aqueousmixtures were then stirred at room temperature until solids precipitate.The solids were filtered, rinsed with water, and dried toprovide solids that were recrystallized from CH2Cl2/hexane to providethe products 27a-p. With the exception of 27d and 27e, theremaining compounds were isolated as inseparable mixtures ofdiastereomers; where possible, the matched pairs of NMR signalsare noted.
  • 30
  • [ 42718-13-8 ]
  • [ 120-36-5 ]
  • [ 1418283-38-1 ]
  • 31
  • [ 42718-13-8 ]
  • [ 555-16-8 ]
  • C16H13FN2O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With gallium(III) bromide In dichloromethane at 30℃; for 0.5h; Molecular sieve; Inert atmosphere;
  • 32
  • [ 42718-13-8 ]
  • [ 555-16-8 ]
  • methyl 4-(4-fluorophenyl)-6-(4-methylphenylsulfonamido)-2-(4-nitrophenyl)-3,4-dihydro-2H-benzo[e][1,3]oxazine-4-carboxylate [ No CAS ]
  • methyl 4-(4-fluorophenyl)-6-(4-methylphenylsulfonamido)-2-(4-nitrophenyl)-3,4-dihydro-2H-benzo[e][1,3]oxazine-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: gallium(III) bromide / dichloromethane / 0.5 h / 30 °C / Molecular sieve; Inert atmosphere 2: gallium(III) bromide / dichloromethane / 48 h / 80 °C / Molecular sieve; Inert atmosphere
  • 33
  • [ 42718-13-8 ]
  • tert-butyl (1-(4-fluorophenyl)-2-(hydroxyamino)-2-oxoethyl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: tetrahydrofuran; water / 20 °C 2: hydroxylamine hydrochloride; potassium hydroxide / methanol / 20 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: tetrahydrofuran; water / 20 °C 2: hydroxylamine hydrochloride; potassium hydroxide / methanol / 20 °C
  • 34
  • [ 42718-13-8 ]
  • N-(1-(4-fluorophenyl)-2-(hydroxyamino)-2-oxoethyl)pivalamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / 20 °C 2: hydroxylamine hydrochloride; potassium hydroxide / methanol / 20 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 20 °C 2: hydroxylamine hydrochloride; potassium hydroxide / methanol / 20 °C
  • 35
  • [ 24424-99-5 ]
  • [ 42718-13-8 ]
  • [ 1273585-65-1 ]
YieldReaction ConditionsOperation in experiment
0.3 g In tetrahydrofuran; water at 20℃; 6 General procedure A: methyl ester and N-Boc protection of amino acids General procedure: The amino acid (1.0 mmol, 1.0 eq) was dispersed in MeOH (1.0 mL per 0.21 mmol of amino acid) with concd H2SO4 (1.8 eq). The mixture was refluxed overnight, at which point LC-MS analysis indicated complete conversion had taken place. The mixture was cooled then concentrated under reduced pressure. The resulting residue was basified with sat. NaHCO3(aq), then extracted with DCM. The combined organic layers were concentrated under reduced pressure. This was taken up into water and THF (5:1), before adding in Boc2O (1.05 eq), and stirring at room temperature overnight. The mixture was diluted with water, before extraction with DCM. Concentration of the combined organic layers gave the desired product.
In tetrahydrofuran; water at 20℃;
  • 36
  • [ 42718-13-8 ]
  • [ 3282-30-2 ]
  • methyl 2-(4-fluorophenyl)-2-pivalamidoacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
0.39 g With triethylamine In dichloromethane at 20℃; for 2h; 11 General procedure B: methyl ester and N-pivamide protection of amino acids General procedure: The amino acid (1.0mmol, 1.0 eq) was dispersed in MeOH (1.0mL per 0.21mmol of amino acid) with concd H2SO4 (1.8 eq). The mixture was refluxed overnight, at which point LC-MS analysis indicated complete conversion had taken place. The mixture was cooled then concentrated under reduced pressure. The resulting residue was basified with sat. NaHCO3(aq), then extracted with DCM. The combined organic layers were concentrated under reduced pressure. The crude compound was taken up in DCM and triethylamine (2.2 eq) was added, followed by pivaloyl chloride (1.1 eq). The reaction mixture was stirred at room temperature for 2h and then diluted with DCM, washed with water and further extracted with DCM. Concentration of the organic layer gave the desired product.
With triethylamine In dichloromethane at 20℃;
  • 37
  • [ 403-42-9 ]
  • [ 42718-13-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: selenium(IV) oxide; pyridine / 110 °C / Inert atmosphere 2.1: thionyl chloride / 13 h / 20 °C / Inert atmosphere; Molecular sieve; Cooling with ice 2.2: Inert atmosphere 3.1: hydroxylamine hydrochloride; sodium acetate / methanol / 3 h / 60 °C / Inert atmosphere 4.1: formic acid; zinc / water; methanol / 8 h / 0 - 20 °C / Inert atmosphere
  • 38
  • [ 156276-23-2 ]
  • [ 42718-13-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: hydroxylamine hydrochloride; sodium acetate / methanol / 3 h / 60 °C / Inert atmosphere 2: formic acid; zinc / water; methanol / 8 h / 0 - 20 °C / Inert atmosphere
  • 39
  • [ 403-32-7 ]
  • [ 42718-13-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: thionyl chloride / 13 h / 20 °C / Inert atmosphere; Molecular sieve; Cooling with ice 1.2: Inert atmosphere 2.1: hydroxylamine hydrochloride; sodium acetate / methanol / 3 h / 60 °C / Inert atmosphere 3.1: formic acid; zinc / water; methanol / 8 h / 0 - 20 °C / Inert atmosphere
  • 40
  • C9H8FNO3 [ No CAS ]
  • [ 42718-13-8 ]
YieldReaction ConditionsOperation in experiment
With formic acid; zinc In methanol; water at 0 - 20℃; for 8h; Inert atmosphere; General procedure for the synthesis of substrates General procedure: Substrate 1a were synthesized from commercially available racemic phenylglycine methyl ester, while other substrates 1b-n were synthesized from related acetophenone derivatives according to the reported procedures.19 A mixture of acetophenone derivative (30mmol) and selenium dioxide (5.0g, 45mmol) in pyridine (15mL) was stirred at 110°C under nitrogen atmosphere overnight. After cooling to room temperature, 4Å molecular sieves (1.8g) and methanol (20mL) were added and the mixture was stirred for additional 10min. Then thionyl chloride (11.3mL, 150mmol) was added dropwise over 1h in an ice-water bath and stirred at room temperature for 12h. Perchloric acid (12mL, 150mmol) in acetonitrile (240mL) and deionized water (24mL) (1:20:2 in volume ratio) were added into the flask, and the mixture was stirred for at least 0.5h. Excess acid was neutralized by saturated sodium bicarbonate, then the mixture was filtrated. After removing the organic solvent by evaporation, the aqueous phase was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuum. The crude product was purified by flash chromatography (silica gel, petrol ether/ethyl acetate=10/1) to obtain arylglyoxylate.19a A mixture of above obtained arylglyoxylate (20mmol), anhydrous sodium acetate (2.0g, 24mmol), hydroxylamine hydrochloride (2.2g, 32mmol) and methanol (70mL) was heated to 60°C for 3h. After evaporating the organic solvent under vacuum, ethyl acetate was added to the resulting residue and the mixture was washed with water. The organic layer was then washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuum to afford oxime. To a solution of oxime (20mmol) and formic acid (24mL) in methanol (40mL) and water (24mL) at 0°C was added Zn dust (3.8g, 60mmol) portion-wise over 1h. The suspension was stirred for 3h at 0°C and an additional 4h at room temperature. The mixture was filtered through Celite and washed with methanol. The filtrate was concentrated and the resulting residue was purified by flash chromatography (silica gel, dichloromethane/methanol=10/1) to afford the racemic arylglycine ester.19b The above obtained arylglycine ester (10mmol) and anhydrous magnesium sulfate (1.2g) were stirred together in dichloromethane (50mL) at room temperature for 20min. Then the aldehyde (10mmol) and triethylamine (8mL) were added sequentially and dropwise. After stirred for 12h at the same temperature, the resulting mixture was filtered and the organic solvent was evaporated in vacuum. The residue was dissolved in ethyl acetate (20mL) and water (20mL), and the separated aqueous layer was extracted with ether (2×20mL). The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuum. The residue was purified by flash chromatography (silica gel, petrol ether/triethylamine=50/1 to 20/1) to afford the substrate for hydrogenation as a white solid.19c
  • 41
  • [ 42718-13-8 ]
  • (R)-methyl 2-(4-fluorophenyl)-2-((2-methoxybenzyl)amino)acetate [ No CAS ]
  • (S)-methyl 2-(4-fluorophenyl)-2-((2-methoxybenzyl)amino)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: magnesium sulfate / dichloromethane / 0.33 h / 20 °C / Inert atmosphere 1.2: 12 h / 20 °C / Inert atmosphere 2.1: [Rh((S)-TCFP)(cod)]BF4; hydrogen / isopropyl alcohol; 2,2,2-trifluoroethanol / 48 h / 20 - 25 °C / 7600.51 Torr / Autoclave; Resolution of racemate
  • 42
  • [ 42718-13-8 ]
  • [ 135-02-4 ]
  • methyl (E)-2-(4-fluorophenyl)-2-((2-methoxybenzylidene)amino)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: α-amino-4-fluorobenzeneacetic acid methyl ester With magnesium sulfate In dichloromethane at 20℃; for 0.333333h; Inert atmosphere; Stage #2: ortho-anisaldehyde With triethylamine In dichloromethane at 20℃; for 12h; Inert atmosphere; General procedure for the synthesis of substrates General procedure: Substrate 1a were synthesized from commercially available racemic phenylglycine methyl ester, while other substrates 1b-n were synthesized from related acetophenone derivatives according to the reported procedures.19 A mixture of acetophenone derivative (30mmol) and selenium dioxide (5.0g, 45mmol) in pyridine (15mL) was stirred at 110°C under nitrogen atmosphere overnight. After cooling to room temperature, 4Å molecular sieves (1.8g) and methanol (20mL) were added and the mixture was stirred for additional 10min. Then thionyl chloride (11.3mL, 150mmol) was added dropwise over 1h in an ice-water bath and stirred at room temperature for 12h. Perchloric acid (12mL, 150mmol) in acetonitrile (240mL) and deionized water (24mL) (1:20:2 in volume ratio) were added into the flask, and the mixture was stirred for at least 0.5h. Excess acid was neutralized by saturated sodium bicarbonate, then the mixture was filtrated. After removing the organic solvent by evaporation, the aqueous phase was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuum. The crude product was purified by flash chromatography (silica gel, petrol ether/ethyl acetate=10/1) to obtain arylglyoxylate.19a A mixture of above obtained arylglyoxylate (20mmol), anhydrous sodium acetate (2.0g, 24mmol), hydroxylamine hydrochloride (2.2g, 32mmol) and methanol (70mL) was heated to 60°C for 3h. After evaporating the organic solvent under vacuum, ethyl acetate was added to the resulting residue and the mixture was washed with water. The organic layer was then washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuum to afford oxime. To a solution of oxime (20mmol) and formic acid (24mL) in methanol (40mL) and water (24mL) at 0°C was added Zn dust (3.8g, 60mmol) portion-wise over 1h. The suspension was stirred for 3h at 0°C and an additional 4h at room temperature. The mixture was filtered through Celite and washed with methanol. The filtrate was concentrated and the resulting residue was purified by flash chromatography (silica gel, dichloromethane/methanol=10/1) to afford the racemic arylglycine ester.19b The above obtained arylglycine ester (10mmol) and anhydrous magnesium sulfate (1.2g) were stirred together in dichloromethane (50mL) at room temperature for 20min. Then the aldehyde (10mmol) and triethylamine (8mL) were added sequentially and dropwise. After stirred for 12h at the same temperature, the resulting mixture was filtered and the organic solvent was evaporated in vacuum. The residue was dissolved in ethyl acetate (20mL) and water (20mL), and the separated aqueous layer was extracted with ether (2×20mL). The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuum. The residue was purified by flash chromatography (silica gel, petrol ether/triethylamine=50/1 to 20/1) to afford the substrate for hydrogenation as a white solid.19c
  • 43
  • [ 1486-48-2 ]
  • [ 42718-13-8 ]
  • methyl 2-(4-fluorophenyl)-2-(3,4,5-tris(benzyloxy)benzamido)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
48% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide Methyl 2-(4-fluorophenyl)-2-(3,4,5-tris(benzyloxy)benzamido)acetate (6i) To a CH2Cl2 solution (3 mL)of 3,4,5-tris(benzyloxy)benzoic acid (390 mg, 0.88 mmol), methyl amino(4-fluorophenyl)acetatehydrochloride (240 mg, 1.09 mmol), EDCI (310 mg, 1.62 mmol), HOBt (70 mg, 0.52 mmol) andTEA (0.57 mL, 3.2 mmol) were added. After stirring overnight, the reaction mixture was dilutedwith ethyl acetate and washed with water and brine, dried over MgSO4 and concentrated underreduced pressure. The residue was purified by flash column chromatography on silica gel (ethylacetate/n-hexane = 1:3) to generate 320 mg of 6i (yield 48%). 1H-NMR (CDCl3) δ 7.46-7.29 (m, 15H),7.29-7.27 (m, 2H), 7.13-7.08 (m, 2H), 7.08-6.99 (m, 2H), 6.99-6.91 (m, 1H), 5.69 (d, J = 6.7 Hz, 1H),5.16-5.12 (m, 4H), 5.10 (s, 2H), 3.79 (s, 3H); 13C-NMR (CDCl3) δ 171.37, 166.04, 163.59, 161.95, 152.82,141.73, 137.35, 136.62, 132.46, 129.12, 129.06, 128.73, 128.59, 128.23, 128.08, 128.01, 127.60, 116.06, 115.92,107.20, 75.18, 71.52, 56.20, 53.07; HRMS (EI) m/z calcd. for 605.2214; found 605.2217.
  • 44
  • [ 7151-76-0 ]
  • [ 42718-13-8 ]
  • methyl 2-(4-fluorophenyl)-2-(4-(methylsulfonamido)benzamido)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
300 mg With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane; N,N-dimethyl-formamide at 20℃;
  • 45
  • [ 42718-13-8 ]
  • N-(1-(4-fluorophenyl)-2-(hydroxyamino)-2-oxoethyl)-4-(methylsulfonamido)benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap / dichloromethane; N,N-dimethyl-formamide / 20 °C 2: hydroxylamine hydrochloride; potassium hydroxide / methanol / 20 °C
  • 46
  • [ 27326-43-8 ]
  • [ 42718-13-8 ]
  • methyl 2-(4-fluorophenyl)-2-(2-vinylbenzamido)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% Stage #1: 2-vinylbenzoic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 1h; Inert atmosphere; Stage #2: α-amino-4-fluorobenzeneacetic acid methyl ester In dichloromethane at 20℃; for 20h; Inert atmosphere;
  • 47
  • [ 42718-13-8 ]
  • 2-(4-fluorophenyl)-2-(2-vinylbenzamido)acetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine / dichloromethane / 1 h / 20 °C / Inert atmosphere 1.2: 20 h / 20 °C / Inert atmosphere 2.1: sodium hydroxide / methanol / 16 h / 20 °C / Inert atmosphere
  • 48
  • [ 42718-13-8 ]
  • 3-(4-fluorophenyl)-9b-methyloxazolo[2,3-a]isoindole-2,5(3H,9bH)-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine / dichloromethane / 1 h / 20 °C / Inert atmosphere 1.2: 20 h / 20 °C / Inert atmosphere 2.1: sodium hydroxide / methanol / 16 h / 20 °C / Inert atmosphere 3.1: dichloro[1,3-di(ethoxycarbonyl)-2,4,5-trimethylcyclopentadienyl]rhodium(III) dimer; copper(II) acetate monohydrate / 1,2-dichloro-ethane / 20 h / 80 °C / Schlenk technique
  • 49
  • [ 42718-13-8 ]
  • 7-chloro-5-methyl-3-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidine [ No CAS ]
  • 2-(4-fluorophenyl)-N-methyl-2-((5-methyl-3-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidin-7-yl)amino)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / 1,4-dioxane / 16 h / 100 °C / Sealed tube 2: triethylamine; trimethyl-(4-trimethylalumanuidyl-1,4-diazoniabicyclo[2.2.2]octan-1-yl)alumanuide / toluene / 16 h / 100 °C
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / 1,4-dioxane / 16 h / 100 °C / Sealed tube 2: triethylamine; trimethyl-(4-trimethylalumanuidyl-1,4-diazoniabicyclo[2.2.2]octan-1-yl)alumanuide / toluene / 16 h / 100 °C
  • 50
  • [ 42718-13-8 ]
  • 7-chloro-5-methyl-3-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidine [ No CAS ]
  • methyl 2-(4-fluorophenyl)-2-((5-methyl-3-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidin-7-yl)amino)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
42% With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 100℃; for 16h; Sealed tube; 2-(4-Fluorophenyl)-N-methyl-2-((5-methyl-3-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidin-7-yl)amino)acetamide (4). Step 1. A mixture of 7-chloro-5-methyl-3-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidine (0.67 g, 2.75 mmol), methyl 2-amino-2-(4-fluorophenyl)acetate (0.50 g, 2.75 mmol) and DIPEA (580 L, 3.3 mmol) in 1,4-dioxane (20 ml) was heated in a sealed tube at 100 °C for 16 h and concentrated in vacuo. The residue was diluted with H2O (ca. 20 ml) and extracted with EtOAc (ca. 50 ml). The organic layer was dried (Na2SO4) and evaporated. Purification of the residue by flash chromatography (EtOAc/petrol ether) gave methyl 2-(4-fluorophenyl)-2-((5-methyl-3-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidin-7-yl)amino)acetate as an off-white solid (0.45 g, 42%). 1H NMR (400 MHz, DMSO-6): δ 8.75 (s, 1H), 8.53 (d, J = 4.0 Hz, 1H), 8.47 (d, J = 8.0 Hz, 1H), 8.13 (d, J = 7.6 Hz, 1H), 7.85-7.82 (m, 1H), 7.77-7.70 (m, 2H), 7.25-7.15 (m, 2H), 7.10 (m, 1H), 6.30 (s, 1H), 5.90 (s, 1H), 3.74 (s, 3H), 2.46 (s, 3H). MS (ESI): m/z 392.0 [M + H]+. Analyt. HPLC: 98.4%.Step 2. A solution of methyl 2-(4-fluorophenyl)-2-((5-methyl-3-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidin-7-yl)amino)acetate (0.15 g, 0.383 mmol) in toluene (3 ml) was treated with methylamine hydrochloride (0.26 g, 3.83 mmol), triethylamine (0.5 ml, 3.83 mmol) and DABAL-Me3 (0.15 g, 0.57 mmol) at 0 °C and heated to 100 °C for 16 h. The mixture was concentrated in vacuo and the residue purified by prep. HPLC to give 2-(4-fluorophenyl)-N-methyl-2-((5-methyl-3-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidin-7-yl)amino)acetamide as an off-white solid (0.06 g, 34%). 1H NMR (400 MHz, DMSO-d6): δ 8.71 (s, 1H), 8.54-8.52 (d, J = 4.8 Hz, 1H), 8.47 (d, J = 7.2 Hz, 1H), 8.42-8.37 (m, 1H), 7.88 (d, J = 6.8 Hz, 1H), 7.83-7.77 (dt, J = 1.6, 7.6 Hz, 1H), 7.65-7.55 (m, 2H), 7.25-7.20 (m, 2H), 7.18-7.12 (m, 1H), 5.97 (s, 1H), 5.43 (d, J = 6.8 Hz, 1H), 2.66 (d, J = 4.4 Hz, 3H), 2.44 (s, 3H). MS (ESI): m/z 391.1 [M + H]+. HR-MS (ESI) for C21H20FN6O: 391.1677 (calc.), 391.1676 (found). Analyt. HPLC: 99.7%.
42% With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 100℃; for 16h; Sealed tube; 2-(4-Fluorophenyl)-N-methyl-2-((5-methyl-3-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidin-7-yl)amino)acetamide (4). Step 1. A mixture of 7-chloro-5-methyl-3-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidine (0.67 g, 2.75 mmol), methyl 2-amino-2-(4-fluorophenyl)acetate (0.50 g, 2.75 mmol) and DIPEA (580 L, 3.3 mmol) in 1,4-dioxane (20 ml) was heated in a sealed tube at 100 °C for 16 h and concentrated in vacuo. The residue was diluted with H2O (ca. 20 ml) and extracted with EtOAc (ca. 50 ml). The organic layer was dried (Na2SO4) and evaporated. Purification of the residue by flash chromatography (EtOAc/petrol ether) gave methyl 2-(4-fluorophenyl)-2-((5-methyl-3-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidin-7-yl)amino)acetate as an off-white solid (0.45 g, 42%). 1H NMR (400 MHz, DMSO-6): δ 8.75 (s, 1H), 8.53 (d, J = 4.0 Hz, 1H), 8.47 (d, J = 8.0 Hz, 1H), 8.13 (d, J = 7.6 Hz, 1H), 7.85-7.82 (m, 1H), 7.77-7.70 (m, 2H), 7.25-7.15 (m, 2H), 7.10 (m, 1H), 6.30 (s, 1H), 5.90 (s, 1H), 3.74 (s, 3H), 2.46 (s, 3H). MS (ESI): m/z 392.0 [M + H]+. Analyt. HPLC: 98.4%.Step 2. A solution of methyl 2-(4-fluorophenyl)-2-((5-methyl-3-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidin-7-yl)amino)acetate (0.15 g, 0.383 mmol) in toluene (3 ml) was treated with methylamine hydrochloride (0.26 g, 3.83 mmol), triethylamine (0.5 ml, 3.83 mmol) and DABAL-Me3 (0.15 g, 0.57 mmol) at 0 °C and heated to 100 °C for 16 h. The mixture was concentrated in vacuo and the residue purified by prep. HPLC to give 2-(4-fluorophenyl)-N-methyl-2-((5-methyl-3-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidin-7-yl)amino)acetamide as an off-white solid (0.06 g, 34%). 1H NMR (400 MHz, DMSO-d6): δ 8.71 (s, 1H), 8.54-8.52 (d, J = 4.8 Hz, 1H), 8.47 (d, J = 7.2 Hz, 1H), 8.42-8.37 (m, 1H), 7.88 (d, J = 6.8 Hz, 1H), 7.83-7.77 (dt, J = 1.6, 7.6 Hz, 1H), 7.65-7.55 (m, 2H), 7.25-7.20 (m, 2H), 7.18-7.12 (m, 1H), 5.97 (s, 1H), 5.43 (d, J = 6.8 Hz, 1H), 2.66 (d, J = 4.4 Hz, 3H), 2.44 (s, 3H). MS (ESI): m/z 391.1 [M + H]+. HR-MS (ESI) for C21H20FN6O: 391.1677 (calc.), 391.1676 (found). Analyt. HPLC: 99.7%.
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