ChemicalBook CAS DataBase List Ivacaftor

Ivacaftor synthesis

7synthesis methods

Product Name:Ivacaftor
CAS Number:873054-44-5
Molecular formula:C24H28N2O3
Molecular Weight:392.49

Ivacaftor, also known as VX-770, is a drug used to treat cystic fibrosis in people with certain mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, who account for 4–5% cases of cystic fibrosis, and is included in a combination drug, lumacaftor/ivacaftor, which is used to treat people with cystic fibrosis who have the F508del mutation in CFTR. Ivacaftor is a "potentiator" of CFTR, meaning it increases the probability that the defective channel will be open and allow chloride ions pass through the channel pore. Synthetic Description Reference: Zhang, Rui; Han, Guanyu; Jiang, Luobin; Shen, Yao; Yang, Rui; Mao, Yongjun; Wang, Hang. An Efficient Synthesis of Ivacaftor. Journal of Heterocyclic Chemistry. Volume 54. Issue 6. Pages 3169-3173. Journal; Online Computer File. (2017). Synthetic Description Reference: Hadida, Sabine; Van Goor, Fredrick; Zhou, Jinglan; Arumugam, Vijayalaksmi; McCartney, Jason; Hazlewood, Anna; Decker, Caroline; Negulescu, Paul; Grootenhuis, Peter D. J. Discovery of N-(2,4-Di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (VX-770, Ivacaftor), a Potent and Orally Bioavailable CFTR Potentiator. Journal of Medicinal Chemistry. Volume 57. Issue 23. Pages 9776-9795. Journal; Online Computer File. (2014). Synthetic Description Reference: He, Yang; Xu, Qien; Ma, Wenpeng; Zhang, Jian; Sun, Hongbing; Shen, Jingshan. Expeditious synthesis of ivacaftor. Heterocycles. Volume 89. Issue 4. Pages 1035-1040. Journal. (2014). Synthetic Description Reference: Vasudevan, N.; Jachak, Gorakhnath R.; Reddy, D. Srinivasa. Breaking and Making of Rings: A Method for the Preparation of 4-Quinolone-3-carb-oxylic Acid Amides and the Expensive Drug Ivacaftor. European Journal of Organic Chemistry. Volume 2015. Issue 34. Pages 7433-7437. Journal; Online Computer File. (2015).

Synthetic Routes

ROUTE 1

ROUTE 2

ROUTE 3

ROUTE 4

Reference: Zhang, Rui; Han, Guanyu; Jiang, Luobin; Shen, Yao; Yang, Rui; Mao, Yongjun; Wang, Hang. An Efficient Synthesis of Ivacaftor. Journal of Heterocyclic Chemistry. Volume 54. Issue 6. Pages 3169-3173. Journal; Online Computer File. (2017).

1246213-45-5 Synthesis

Carbonic acid 5-[[(1,4-dihydro-4-oxo-3-quinolinyl)carbonyl]amino]-2,4-bis(1,1-dimethylethyl)phenyl methyl ester

1246213-45-5
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873054-44-5
288 suppliers
$28.00/1unit

Yield:873054-44-5 76%

Reaction Conditions:

with water;sodium hydroxide in methanol at 20; for 5 h;

Steps:

28 Example 28: Synthesis of ivacaftor (26):
To a solution of 2,4-di-tert-butyl-5-(4-oxo-1,4-dihydroquinoline-3-carboxamido)phenyl methyl carbonate 5 (30 mg, 0.06mmol) in MeOH (2 mL) was added NaOH (5.3 mg, 0.13mmol) dissolved in H₂O (2 mL), and the reaction mixture was stirred at room temperature for 5h. Reaction mass was evaporated to one third of its volume (temperature not exceeding 40°C) and acidified with aq.2N HC1 to pH 2-3. The resulting precipitate was collected by suction filtration give desired compound 7 (19 mg, 76%) as off white solid. 1H NMR (400MHz, DMSO-d₆) δ = 12.88 (d, J = 6.6 Hz, 1 H), 11.81 (s, 1 H), 9.20 (s, 1 H), 8.86 (d, J = 6.6 Hz, 1 H), 8.32 (d, J = 7.8 Hz, 1 H), 7.88 - 7.65 (m, 2 H), 7.51 (t, J = 7.5 Hz, 1 H), 7.16 (s, 1 H), 7.10 (s, 1 H), 1.38 (s,9H), 1.36 (s, 9H).

References:

COUNCIL OF SCIENTIFIC & INDUSTRIAL RESEARCH;REDDY, Dumbala Srinivasa;NATARAJAN, Vasudevan;JACHAK, Gorakhnath Rajaram WO2016/181414, 2016, A1 Location in patent:Paragraph 066

FullText

873055-58-4 Synthesis

873055-58-4
144 suppliers
$40.00/100mg

13721-01-2 Synthesis

4-OXO-1,4-DIHYDROQUINOLINE-3-CARBOXYLIC ACID

13721-01-2
252 suppliers
$11.00/250mg

873054-44-5
288 suppliers
$28.00/1unit

References

5-amino-2,4-di-tert-butylphenyl methyl carbonate

1182822-31-6
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13721-01-2 Synthesis

13721-01-2
252 suppliers
$11.00/250mg

873054-44-5
288 suppliers
$28.00/1unit

References

873055-58-4 Synthesis

873055-58-4
144 suppliers
$40.00/100mg

873054-44-5
288 suppliers
$28.00/1unit

References

3-Quinolinecarboxamide, N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxo-1-(phenylmethyl)-

1622228-86-7
1 suppliers
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873054-44-5
288 suppliers
$28.00/1unit

References

Ivacaftor Related Search:

Iodixanol Voriconazole Bumetanide 6-Mercaptopurine Atazanavir Telaprevir Rapamycin CFTRinh-172 4-OXO-1,4-DIHYDROQUINOLINE-3-CARBOXYLIC ACID 5-AMino-2,4-di-tert-butylphenol