873054-44-5
- Product Name：Ivacaftor
- Molecular Formula：C24H28N2O3
- Purity：99%
- Molecular Weight：392.498
Product Details;
CasNo： 873054-44-5
Molecular Formula： C24H28N2O3
Cost-effective and customizable Ivacaftor 873054-44-5 for sale
- Molecular Formula:C24H28N2O3
- Molecular Weight:392.498
- Vapor Pressure:1E-12mmHg at 25°C
- Refractive Index:1.605
- Boiling Point:550.4 °C at 760 mmHg
- PKA:11.08±0.23(Predicted)
- Flash Point:286.7 °C
- PSA：85.68000
- Density:1.187 g/cm3
- LogP:5.46500
VX-770(Cas 873054-44-5) Usage
|
Synthesis |
Several patents describe a synthesis of ivacaftor, only one demonstrates the synthesis on scale and includes yields, which is depicted in the scheme. Beginning with treatment of commercial di-tert-butylphenol derivative 91 with ethyl chloroformate, the synthesis of carbonate 92 was achieved in quantitative yield. Nitration of 92 provided the desired nitroarene regioisomer 93 in 57% yield which was isolated by recrystallization. Reduction of the newlyinstalled nitro group and subsequent amide bond formation via reaction with commercially available acid chloride 94 produced amide 95 in 53% yield over the two step sequence. Finally, cleavage of the carbonate unmasked the phenol to furnish ivacaftor (XV) in 96% yield. |
|
references |
1. van goor f1, hadida s, grootenhuis pd, burton b, cao d, neuberger t, turnbull a, singh a, joubran j, hazlewood a, zhou j, mccartney j,arumugam v, decker c, yang j, young c, olson er, wine jj, frizzell ra, ashlock m, negulescu p. rescue of cf airway epithelial cell function in vitro by a cftr potentiator, vx-770. proc natl acad sci u s a. 2009 nov 3;106(44):18825-30. 2. vachel l1, norez c, becq f, vandebrouck c. effect of vx-770 (ivacaftor) and oag on ca2+ influx and cftr activity in g551d and f508del-cftr expressing cells. j cyst fibros. 2013 dec;12(6):584-91 |
|
Definition |
ChEBI: An aromatic amide obtained by formal condensation of the carboxy group of 4-oxo-1,4-dihydroquinoline-3-carboxylic acid with the amino group of 5-amino-2,4-di-tert-butylphenol. Used for the treatment of cystic fibrosis. |
|
Brand name |
Kalydeco |
InChI:InChI=1/C24H28N2O3/c1-23(2,3)16-11-17(24(4,5)6)20(27)12-19(16)26-22(29)15-13-25-18-10-8-7-9-14(18)21(15)28/h7-13,27H,1-6H3,(H,25,28)(H,26,29)
873054-44-5 Relevant articles
Pharmaceutical compositions for the treatment of cystic fibrosis transmembrane conductance regulator mediated diseases
-
, (2021/04/21)
The present invention features compositi...
METHODS OF TREATMENT FOR CYSTIC FIBROSIS
-
, (2020/06/05)
This application describes methods of tr...
METHODS OF TREATMENT FOR CYSTIC FIBROSIS
-
, (2020/12/11)
This application describes methods of tr...
Utilizing o-Quinone Methide Chemistry: Synthesis of d9-Ivacaftor
Lewandowski, Bérénice L.,Looker, Adam R.,Roeper, Stefanie,Ryan, Michael P.,Wilde, Nathan,Ye, Zhifeng
, (2020/01/22)
Lead time and cost are important factors...
873054-44-5 Process route
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C31H34N2O3
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873054-44-5,1174930-71-2
ivacaftor
| Conditions | Yield |
|---|---|
|
With
5%-palladium/activated carbon; hydrogen;
In
methanol;
at 35 ℃;
for 5h;
under 1520.1 Torr;
Temperature;
Pressure;
|
80% |
-
-
873055-58-4
5-amino-2-4-di-tert-butyl-phenol
-
-
13721-01-2
4-oxo-1,4-dihydroquinoline-3-carboxylic acid
-
-
873054-44-5,1174930-71-2
ivacaftor
| Conditions | Yield |
|---|---|
|
With
O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine;
In
N,N-dimethyl-formamide;
|
71% |
|
With
triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate;
In
dichloromethane;
at 25 ℃;
for 12h;
|
71% |
|
With
benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine;
In
N,N-dimethyl-formamide;
at 20 ℃;
|
71% |
|
4-oxo-1,4-dihydroquinoline-3-carboxylic acid;
With
O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine;
In
N,N-dimethyl-formamide;
at 20 ℃;
for 0.166667h;
5-amino-2-4-di-tert-butyl-phenol;
In
N,N-dimethyl-formamide;
at 20 ℃;
|
52% |
|
4-oxo-1,4-dihydroquinoline-3-carboxylic acid;
With
O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine;
In
N,N-dimethyl-formamide;
at 20 ℃;
for 0.166667h;
5-amino-2-4-di-tert-butyl-phenol;
In
N,N-dimethyl-formamide;
at 20 ℃;
|
52% |
|
4-oxo-1,4-dihydroquinoline-3-carboxylic acid;
With
O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine;
In
N,N-dimethyl-formamide;
at 20 ℃;
for 0.166667h;
5-amino-2-4-di-tert-butyl-phenol;
In
N,N-dimethyl-formamide;
at 20 ℃;
|
52% |
|
4-oxo-1,4-dihydroquinoline-3-carboxylic acid;
With
O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine;
In
N,N-dimethyl-formamide;
at 20 ℃;
for 0.166667h;
5-amino-2-4-di-tert-butyl-phenol;
In
N,N-dimethyl-formamide;
at 20 ℃;
|
52% |
|
4-oxo-1,4-dihydroquinoline-3-carboxylic acid;
With
O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine;
In
N,N-dimethyl-formamide;
at 20 ℃;
for 0.166667h;
5-amino-2-4-di-tert-butyl-phenol;
In
N,N-dimethyl-formamide;
at 20 ℃;
|
52% |
|
4-oxo-1,4-dihydroquinoline-3-carboxylic acid;
With
O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine;
In
N,N-dimethyl-formamide;
at 20 ℃;
for 0.166667h;
5-amino-2-4-di-tert-butyl-phenol;
In
N,N-dimethyl-formamide;
at 20 ℃;
|
52% |
|
4-oxo-1,4-dihydroquinoline-3-carboxylic acid;
With
O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine;
In
N,N-dimethyl-formamide;
at 20 ℃;
for 0.166667h;
5-amino-2-4-di-tert-butyl-phenol;
In
N,N-dimethyl-formamide;
at 20 ℃;
|
52% |
|
4-oxo-1,4-dihydroquinoline-3-carboxylic acid;
With
O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine;
In
N,N-dimethyl-formamide;
at 20 ℃;
for 0.166667h;
5-amino-2-4-di-tert-butyl-phenol;
In
N,N-dimethyl-formamide;
at 20 ℃;
|
52% |
|
4-oxo-1,4-dihydroquinoline-3-carboxylic acid;
With
O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine;
In
N,N-dimethyl-formamide;
at 20 ℃;
for 0.166667h;
5-amino-2-4-di-tert-butyl-phenol;
In
N,N-dimethyl-formamide;
at 20 ℃;
|
52% |
|
4-oxo-1,4-dihydroquinoline-3-carboxylic acid;
With
O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine;
In
N,N-dimethyl-formamide;
at 20 ℃;
for 0.166667h;
5-amino-2-4-di-tert-butyl-phenol;
In
N,N-dimethyl-formamide;
at 20 ℃;
|
52% |
|
4-oxo-1,4-dihydroquinoline-3-carboxylic acid;
With
O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine;
In
N,N-dimethyl-formamide;
at 15 - 30 ℃;
for 0.166667h;
5-amino-2-4-di-tert-butyl-phenol;
In
N,N-dimethyl-formamide;
at 15 - 30 ℃;
|
52% |
|
4-oxo-1,4-dihydroquinoline-3-carboxylic acid;
With
O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine;
In
N,N-dimethyl-formamide;
at 20 ℃;
for 0.166667h;
5-amino-2-4-di-tert-butyl-phenol;
In
N,N-dimethyl-formamide;
at 20 ℃;
|
52% |
|
4-oxo-1,4-dihydroquinoline-3-carboxylic acid;
With
O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine;
In
N,N-dimethyl-formamide;
at 20 ℃;
for 0.166667h;
5-amino-2-4-di-tert-butyl-phenol;
In
N,N-dimethyl-formamide;
at 20 ℃;
|
52% |
|
4-oxo-1,4-dihydroquinoline-3-carboxylic acid;
With
O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine;
In
N,N-dimethyl-formamide;
at 20 ℃;
for 0.166667h;
5-amino-2-4-di-tert-butyl-phenol;
In
N,N-dimethyl-formamide;
at 20 ℃;
|
52% |
|
4-oxo-1,4-dihydroquinoline-3-carboxylic acid;
With
N-ethyl-N,N-diisopropylamine; HATU;
In
N,N-dimethyl-formamide;
at 25 ℃;
for 0.166667h;
5-amino-2-4-di-tert-butyl-phenol;
In
N,N-dimethyl-formamide;
at 25 ℃;
for 12h;
|
46% |
|
4-oxo-1,4-dihydroquinoline-3-carboxylic acid;
With
N-ethyl-N,N-diisopropylamine; HATU;
In
N,N-dimethyl-formamide;
for 0.5h;
5-amino-2-4-di-tert-butyl-phenol;
In
N,N-dimethyl-formamide;
for 15h;
|
873054-44-5 Upstream products
-
873055-58-4
5-amino-2-4-di-tert-butyl-phenol
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1246213-45-5
2,4-di-tert-butyl-5-(4-oxo-1,4-dihydroquinoline-3-carboxamido)phenyl methyl carbonate
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134271-94-6
3-methyl-4-nitro-1H-indole
-
1182822-31-6
5-amino-2,4-di-tert-butylphenyl methyl carbonate
873054-44-5 Downstream products
-
943316-05-0
[5-[(4-oxo-1H-quinolin-3-yl)carbonylamino]-2,4-ditert-butyl-phenyl] 2-diethylaminoacetate
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1134821-98-9
ivacaftor 2-methylbutyric acid solvate
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1134821-99-0
N-(2,4-di-tert-butyl-5-hydroxyphenyl)-1,4-dihydro-4-oxoquinoline-3-carboxamide propylene glycol solvate
-
1134822-01-7
N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide.lactic acid
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-
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