KPT-330 synthesis

6synthesis methods

Product Name:KPT-330
CAS Number:1393477-72-9
Molecular formula:C17H11F6N7O
Molecular Weight:443.31

Selinexor, also known as KPT-330, is an orally bioavailable, potent and selective XPO1/CRM1 Inhibitor. Selinexor is effective in acquired resistance to ibrutinib and synergizes with ibrutinib in chronic lymphocytic leukemia. Selinexor potentiates the antitumor activity of gemcitabine in human pancreatic cancer through inhibition of tumor growth, depletion of the antiapoptotic proteins, and induction of apoptosis. Selinexor has strong activity against primary AML cells while sparing normal stem and progenitor cells. Synthetic Description Reference: Muthusamy, Anantha Rajmohan; Kanniah, Sundara Lakshmi; Ravi, Akash; Das, Tonmoy Chitta; Chemate, Rajendra Popat; Singh, Anil Kumar; Wagh, Yogesh Dhananjay. Novel crystalline forms of selinexor and process for their preparation. Assignee Watson Laboratories Inc., USA. WO 2018129227. (2018). Synthetic Description Reference: Chen, Xinying; Xu, Liang; Liu, Wenzhong. Synthesis method of selinexor bulk pharmaceutical. Assignee Guangzhou Wenhao Biotechnology Co., Ltd., Peop. Rep. China. CN 106831731. (2017). Synthetic Description Reference: Sandanayaka, Vincent P.; Shacham, Sharon; McCauley, Dilara; Shechter, Sharon. Preparation of hydrazide containing nuclear transport modulators and uses thereof. Assignee Karyopharm Therapeutics, Inc., USA. WO 2013019548. (2013).

Synthetic Routes

ROUTE 1

ROUTE 2

ROUTE 3

Reference: Muthusamy, Anantha Rajmohan; Kanniah, Sundara Lakshmi; Ravi, Akash; Das, Tonmoy Chitta; Chemate, Rajendra Popat; Singh, Anil Kumar; Wagh, Yogesh Dhananjay. Novel crystalline forms of selinexor and process for their preparation. Assignee Watson Laboratories Inc., USA. WO 2018129227. (2018).

(Z)-3-(3-(3,5-bis(trifluoroMethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid

1388842-44-1
40 suppliers
inquiry

54608-52-5 Synthesis

54608-52-5
226 suppliers
$9.00/1g

1393477-72-9
138 suppliers
$29.00/1mg

Yield:1393477-72-9 83%

Reaction Conditions:

with 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride in ethyl acetate;acetonitrile at 0 - 25; for 3 h;Solvent;Temperature;

Steps:

28 Example 28: Preparation of Selinexor
In a 3-L, 3-necked, round-bottomed flask were charged 60.0 gr (Z)-3-(3-(3,5- bis(trifluoromethyl)phenyl)- 1 H- 1,2, 4-triazol- 1 -yl)acrylic acid (SLN- 105, prepared according to examples 27), Ethyl acetate (0.42 lit, 7V) and Acetonitrile (0.3 lit,5V) at 20-25°C. Charged 2-hydrazino pyrazine (19.8 gr, 1.05 eq) then cooled to 0 to 5°C. Charged EDC .HC1 (1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride) (49. lgr 1 .Seq) at 0 to 5°C. The reaction mass was stirred for 3hrs and monitored by HPLC (till SLN-105 NMT 1.0%). Once the reaction completes, charge water (0.2lit, 2V) and stirred for 15-30 mm at 15-20°C, settled and separated the organic layer. Collected the organic layer and washed with sodium bicarbonate solution (0.Slit, SV). Finally washed the organic layer with water (0.2lit, 2 V) and combined the collected organic layer containing the product. The solvent is distilled off under vacuum at 50 to 60°C for 30 mm. To the obtained solid, added absolute Ethanol (0.6lit, 1OV) and stirred for 30mm at 20-25°C then cooled to 0-5°C and stirred for 1 hr at 0-5°C. Filtered the compound under vacuum at 20-25°C and washed with Ethanol (0.2lit, 2V). The wet cake was dried at 55-60°C under vacuum (600 to 700 mm Hg) for 4 hrs. (Yield 83%).

References:

WATSON LABORATORIES INC.;MUTHUSAMY, Anantha Rajmohan;KANNIAH, Sundara Lakshmi;RAVI, Akash;DAS, Tonmoy Chitta;CHEMATE, Rajendra Popat;SINGH, Anil Kumar;WAGH, Yogesh Dhananjay WO2018/129227, 2018, A1 Location in patent:Paragraph 00196; 00197; 00215; 00216; 00218

FullText