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Chemical Structure| 117924-33-1 Chemical Structure| 117924-33-1

Structure of 117924-33-1

Chemical Structure| 117924-33-1

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Product Details of [ 117924-33-1 ]

CAS No. :117924-33-1
Formula : C12H28NO2P
M.W : 249.33
SMILES Code : CCN(CC)P(OC(C)(C)C)OC(C)(C)C
MDL No. :MFCD00134307
InChI Key :KUKSUQKELVOKBH-UHFFFAOYSA-N
Pubchem ID :4251849

Safety of [ 117924-33-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H227-H315-H319-H335
Precautionary Statements:P305+P351+P338

Application In Synthesis of [ 117924-33-1 ]

* 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 [ 117924-33-1 ]

[ 117924-33-1 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 722544-51-6 ]
  • [ 117924-33-1 ]
  • di-tert-butyl 2-[[3-({4-[(5-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-3-yl)amino]quinazolin-7-yl}oxy)propyl](ethyl)amino]ethyl phosphite [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine hydrochloride; In N,N-dimethyl acetamide; at -20 - -10℃; for 4h;Product distribution / selectivity; Preparation of mono(tert-butyl) 2-[[3-([4-[(5-[2-[(3-fluorophenyl)amino]-2-oxoethyl]-1H-pyrazol-3-yl)amino]-quinazolin-7-yl]oxy)propyl](ethyl)amino]ethyl phosphate [AZD1152 t-Bu P(5)ester] 2-{3-[(7-{3-[Ethyl(2-hydroxyethyl)amino]propoxy}-quinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide and pyridine.hydrochloride were mixed in N,N-dimethylacetamide and the solution chilled to -15° C. Di-tert-butyl diethylphosphoramidite (1.5-2.1 molar equivalents) was then added whilst the temperature was maintained. The reaction mixture was treated in situ with 30percent w/w hydrogen peroxide (about 4.2 mole equivalents) whilst the temperature was kept below ambient temperature. Remaining hydrogen peroxide was destroyed by the addition of sodium metabisulphite (as a 10percent w/v solution) whilst maintaining the temperature below 40° C. The resulting solution of di-tert-butyl 2-[[3-({4-[(5-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-3-yl)amino]quinazolin-7-yl}oxy)propyl](ethyl)amino]ethyl phosphate was then heated to 40° C. and sodium hydroxide solution (2M) added to adjust to pH 5-6.5. The temperature and pH was maintained for a period of about 90 minutes with seeding. Water was then charged and the pH adjusted further to within the range pH 8-9 to optimise the recovery. The warm reaction mixture was filtered directly to afford mono-tert-butyl 2-[[3-({4-[(5-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-3-yl)amino]quinazolin-7-yl}oxy)propyl](ethyl)amino]ethyl phosphate which washed with a mixture of N,N-dimethylacetamide/water and water and finally dried (in vacuo or a stream of a suitable inert gas) to afford mono(tert-butyl) 2-[[3-({4-[(5-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-3-yl)amino]-quinazolin-7-yl}oxy)propyl](ethyl)amino]ethyl phosphate as an off-white solid at a yield of between 86-93percent. 1H-NMR (DMSO d6): 10.48 (s, 1H), 9.75 (br s, 1H), 8.98 (s, 1H), 8.85 (d, 1H), 7.67 (pr of m, 1H), 7.48(pr of d, 1H), 7.37 (m, 2H), 7.3 (d, 1H), 6.87 (m, 1H), 6.83 (s, 1H), 4.34 (t, 2H), 4.28 (m, 2H), 3.88 (s, 2H), 3.53 (m, 2H), 3.43 (m, 2H), 3.33 (m, 2H), 2.3 (m, 2H), 1.47 (s, 9H), 1.32 (t, 3H): MS (+ve ESI): (M+H)+ 644.2761 fragment (less butyl) 588.2147 Preparation of mono(tert-butyl) 2-[[3-([4-[(5-[2-[(3-fluorophenyl)amino]-2-oxoethyl]-1H-pyrazol-3-yl)amino]-quinazolin-7-yl]oxy)propyl](ethyl)amino]ethyl phosphate [AZD1152 t-Bu P(5)ester]-Alternative RouteTo a slurry of pyridine.hydrochloride in N,N-dimethylacetamide was charged a solution of 2-{3-[(7-{3-[Ethyl(2-hydroxyethyl)amino]propoxy}-quinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide and di-tert-butyl diethylphosphoramidite (ideally 1 molar equivalents) in N,N-dimethylacetamide over an extended period (ideally 3 hours) and maintaining the temperature between -20 to -10° C. (ideally -15° C.). This is followed by the further addition of di-tert-butyl diethylphosphoramidite (ideally 0.5 molar equivalents) during a period of 1 hour also maintaining the temperature between -20 to -10° C. (ideally -15° C.).The reaction mixture is treated in situ with 30percent w/w hydrogen peroxide (about 4.2 mole equivalents) whilst the temperature was kept below -10° C. (ideally -12 to -8° C.) and held for a period at this temperature (ideally 16 hours). Remaining hydrogen peroxide is destroyed by the addition of sodium metabisulphite (as a 10percent w/v aqueous solution) whilst maintaining the temperature below 40° C.The resulting solution of di-tert-butyl 2-[[3-({4-[(5-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-3-yl)amino]quinazolin-7-yl}oxy)propyl](ethyl)amino]ethyl phosphate was then heated to 40° C. and sodium hydroxide solution (ideally 2M) added to adjust to pH 5.5-6.5 (ideally pH 6) with seeding with suitably crystalline material. The temperature is held and a range of pH 5-6 maintained by the addition of extra sodium hydroxide solution for a period of at least 2 hours. Water is then charged and the pH adjusted further to within the range pH 8-9 (ideally pH 8.8) whilst maintaining the temperature (ideally 40° C. but within range 35-45° C.) for a period of 16 hours so as to optimise the recovery. The warm reaction mixture is filtered directly to afford mono-tert-butyl 2-[[3-({4-[(5-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-3-yl)amino]quinazolin-7-yl}oxy)propyl](ethyl)amino]ethyl phosphate which washed several times with water and finally dried (either in vacuo or a stream of a suitable inert gas) to afford the mono(tert-butyl) 2-[[3-({4-[(5-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-3-yl)amino]-quinazolin-7-yl}oxy)propyl](ethyl)amino]ethyl phosphate as an off-white solid at a yield of between 86-93percent.1H-NMR (DMSO d6): 10.48 (s, 1H), 9.75 (br s, 1H), 8.98 (s, 1H), 8.85 (d, 1H), 7.67 (pr of m, 1H), 7.48(pr of d, 1H), 7.37 (m, 2H), 7.3 (d, 1H), 6.87 (m, 1H), 6.83 (s, 1H), 4.34 (t, 2H), 4.28 (m, 2H), 3.88 (s, 2H), 3.53 (m, 2H), 3.43 (m, 2H), 3.33 (m, 2H), 2.3 (m, 2H), 1.47 (s, 9H), 1.32 (t, 3H):MS (+ve...
  • 2
  • [ 722544-51-6 ]
  • [ 117924-33-1 ]
  • [ 722544-50-5 ]
YieldReaction ConditionsOperation in experiment
Di-terf-butyl-diethylphosphoramidite (417 mum, 1.5 mmol) was slowly added to a solution of 2- {3-[(7- {3-[ethyl(2-hydroxyethyl)amino]propoxy} quinazolin-4-yl)amino]-lH- pyrazol-5-yl}- N-(3-fluorophenyl)acetamide in dimethylformamide in the presence of tetrazole at ambient temperature under argon. The mixture was stirred at ambient temperature for 1.5 hours, cooled to -10 0C and hydrogen peroxide (9.0 nu solution) was slowly added. The resulting mixture was stirred at ambient temperature for 2 hours. Sodium metabisulphite in water was then added at 0 0C and the mixture was stirred at <n="23"/>ambient temperature for 0.5 hour. The mixture was concentrated, dichloromethane / methanol (8:2) was added before the solid was filtered and washed with dichloromethane / methanol. Concentration of the filtrate in vacuo followed by chromatography on silica gel, eluting with dichloromethane / methanol (90:10) to dichloromethane / methanol / ammonia (7.0 N) (90:10:1), yielded di-ter/-butyl 2-[[3-({4-[(5-{2-[(3-fluorophenyl)amino]-2- oxoethyl}-lH-pyrazol-3-yl)amino]quinazolin-7-yl}oxy)propyl](ethyl)amino]ethyl phosphate as a pale yellow solid.
2-{3-[(7-{3-[Ethyl(2-hydroxyethyl)amino]propoxy}-quinazolin-4-yl)amino]-lH-pyrazol- 5-yl}- N-(3-fluorophenyl)acetamide and pyridine.hydrochloride were mixed in N, N- dimethylacetamide and the solution chilled to -150C. Di-tert-butyl diethylphosphoramidite (1.5 - 2.1 molar equivalents) was then added whilst the temperature was maintained. The reaction mixture was treated in situ with 30percent w/w hydrogen peroxide (about 4.2 mole equivalents) whilst the temperature was kept below ambient temperature. Remaining hydrogen peroxide was destroyed by the addition of sodium metabisulphite (as a 10percent w/v solution) whilst maintaining the temperature below 4O0C. The resulting solution of di-fert-butyl 2-[[3-({4-[(5-{2-[(3-fluorophenyl)amino]-2- oxoethyl}-lH-pyrazol-3-yl)amino]quinazolin-7-yl}oxy)propyl](ethyl)amino]ethyl phosphate was then heated to 4O0C and sodium hydroxide solution (2M) added to adjust to peta 5 - 6.5. The temperature and peta was maintained for a period of about 90 minutes with seeding. Water was then charged and the peta adjusted further to within the range peta 8 - 9 to optimise the recovery. The warm reaction mixture was filtered directly to afford mono- tert-butyl 2-[[3-({4-[(5-{2-[(3-fiuorophenyl)amino]-2-oxoethyl}-lH-pyrazol-3- yl)amino]quinazolin-7-yl}oxy)propyl](ethyl)amino]ethyl phosphate which was washed with a mixture of N,N-dimethylacetamide/water and water and finally dried (in vacuo or a stream of a suitable inert gas) to afford mono(fert-butyl) 2-[[3-({4-[(5-{2-[(3- fluorophenyl)amino]-2-oxoethyl}-lH-pyrazol-3-yl)amino]-quinazolin-7- yl}oxy)propyl](ethyl)amino]ethyl phosphate as an off-white solid at a yield of between 86 - 93percent.1H-NMR (DMSO d6): 10.48 (s, IH), 9.75 (br s, IH), 8.98 (s, IH), 8.85 (d, IH), 7.67 (pr of m, IH), 7.48(pr of d, IH), 7.37 (m, 2H), 7.3 (d, IH), 6.87 (m, IH), 6.83 (s, IH), 4.34 (t, <n="28"/>2H), 4.28 (m, 2H), 3.88 (s, 2H), 3.53 (m, 2H), 3.43 (m, 2H), 3.33 (m, 2H), 2.3 (m, 2H),1.47 (s, 9H), 1.32 (t, 3H):MS (+ve ESI) : (M+H)+ 644.2761 fragment (less butyl) 588.2147; To a slurry of pyridine.hydrochloride in N,N-dimethylacetamide was charged a solution of 2-{3-[(7-{3-[Ethyl(2-hydroxyethyl)amino]propoxy}-quinazolin-4-yl)amino]-lH-pyrazol- 5-yl}- N-(3-fluorophenyl)acetamide and di-ter/-butyl diethylphosphoramidite (ideallyl molar equivalents) in N,N-dimethylacetamide over an extended period (ideally 3 hours) and maintaining the temperature between -20 to -100C (ideally -150C). This is followed by the further addition of di-tert-hutyl diethylphosphoramidite (ideally 0.5 molar equivalents) during a period of 1 hour also maintaining the temperature between -20 to -1O0C (ideally - 15°C).The reaction mixture is treated in situ with 30percent w/w hydrogen peroxide (about 4.2 mole equivalents) whilst the temperature was kept below -1O0C (ideally -12 to -8°C) and held for a period at this temperature (ideally 16 hours). Remaining hydrogen peroxide is destroyed by the addition of sodium metabisulphite (as a 10percent w/v aqueous solution) whilst maintaining the temperature below 4O0C.The resulting solution of di-tert-butyl 2-[[3-({4-[(5-{2-[(3-fluororhohenyl)amino]-2- oxoethyl} - lH-pyrazol-3-yl)amino]quinazolin-7-yl} oxy)propyl](ethyl)amino] ethyl phosphate was then heated to 400C and sodium hydroxide solution (ideally 2M) added to adjust to peta 5.5 - 6.5 (ideally peta 6) with seeding with suitably crystalline material. The temperature is held and a range of peta 5-6 maintained by the addition of extra sodium hydroxide solution for a period of at least 2 hours. Water is then charged and the peta adjusted further to within the range peta 8 - 9 (ideally peta 8.8) whilst maintaining the temperature (ideally 4O0C but within range 35 - 450C) for a period of 16 hours so as to optimise the recovery. The warm reaction mixture is filtered directly to afford mono-tert- butyl 2-[[3-({4-[(5-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-lH-pyrazol-3- yl)amino]quinazolin-7-yl}oxy)propyl](ethyl)amino]ethyl phosphate which was washed <n="29"/>several times with water and finally dried (either in vacuo or a stream of a suitable inert gas) to afford the mono(/er/-butyl) 2-[[3-({4-[(5-{2-[(3-fluorophenyl)amino]-2-oxoethyl}- lH-pyrazol-3-yl)amino]-quinazolin-7-yl}oxy)propyl](ethyl)amino]ethyl phosphate as an off-white solid at a yield of between 86 - 93percent.1H-NMR (DMSO d6): 10.48 (s, IH), 9.75 (br s, IH), 8.98 (s, IH), 8.85 (d, IH), 7.67 (pr of m, IH), 7.48(pr of d, IH), 7.37 (m, 2H), 7.3 (d, IH), 6.87 (m, IH), 6.83 (s, IH), 4.34 (t,2H), 4.28 (m, 2H)5 3.88 (s, 2H), 3.53 (m, 2H)5 3.43 (m, 2H), 3.33 (m, 2H), 2.3 (m, 2H),1.47 (s, 9H), 1.32 (t, 3H):MS (+ve ESI) : (M+H)+ 644.2761 fragment (less butyl) 588.2147.
 

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