ChemicalBook CAS DataBase List Deucravacitinib

Deucravacitinib synthesis

10synthesis methods

Product Name:Deucravacitinib
CAS Number:1609392-27-9
Molecular formula:C20H22N8O3
Molecular Weight:422.45

Lewis acid-mediated SNAr reaction of pyridazine 15.12 and aniline 15.7 gave 15.13 in 95% yield with excellent regioselectivity (～185:1 15.13:15.14). Although an unconventional compound, 15.13 was isolated as a Zn-dicarboxylate due to its good solubility, ease of crystallization and isolation. The aryl pyridazine 15.13 then formed a C-N bond with amide 15.15 under Pd catalysis to afford the penultimate carboxylate 15.16 in 94% yield. Trideuterated methylamides were generated under standard amide coupling conditions. Deucravacitinib was prepared in 75% yield by crystallization in NMP and i-PrOH.

6228-73-5 Synthesis

6228-73-5
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1609394-23-1
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1609392-27-9
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Yield:1609392-27-9 46%

Reaction Conditions:

with tris-(dibenzylideneacetone)dipalladium⁽⁰⁾;caesium carbonate;4,5-bis(diphenylphosphino)-9,9-dimethylxanthene in 1,4-dioxane at 130; for 2.33333 h;Sealed tube;Inert atmosphere;

Steps:

52.2 Example
Step 2[00220j Intl3 (2.32 g, 6.16 mmol) and cyclopropanecarboxamide (1.048 g, 12.31 mmol) were dissolved in dioxane (62 mL) and Pd2(dba)3 (564 mg, 0.6 16 mmol), Xantphos (534 mg, 0.924 mmol) and cesium carbonate (4.01 g, 12.3 mmol) were added.The vessel was evacuated three times (backfilling with nitrogen) and then sealed and heated to 130 °C for 140 minutes. The reaction was filtered through CELITE (eluting with ethyl acetate) and concentrated (on smaller scale this material could then be purified using preparative HPLC). The crude product was adsorbed onto CELITE using dichloromethane, dried and purified using automated chromatography (100% EtOAc)provide example 52 (1.22 g, 46% yield). ‘H NMR (500MHz, chloroform-d) ? 10.99 (s,1H), 8.63 (s, 1H), 8.18 (s, 1H), 8.10 (d, J=0.5 Hz, 2H), 7.81 (dd, J7.9, 1.7 Hz, 1H), 7.51(dd, J7.9, 1.4 Hz, 1H), 7.33 - 7.20 (m, 7H), 4.01 (d, J0.3 Hz, 3H), 3.82 (s, 3H), 1.73 -1.60 (m, 1H), 1.16 - 1.06 (m, 2H), 0.97 - 0.84 (m, 2H). LC retention time 6.84 [N].MS(Ej m/z: 426 (MHj

References:

BRISTOL-MYERS SQUIBB COMPANY;MOSLIN, Ryan M.;WEINSTEIN, David S.;WROBLESKI, Stephen T.;TOKARSKI, John S.;KUMAR, Amit WO2014/74661, 2014, A1 Location in patent:Paragraph 00220

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1609394-10-6 Synthesis