2,5,6-trichloronicotinaMide synthesis
- Product Name:2,5,6-trichloronicotinaMide
- CAS Number:142266-62-4
- Molecular formula:C6H3Cl3N2O
- Molecular Weight:225.46
54718-39-7
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$11.00/250mg
142266-62-4
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$121.00/100mg
Yield:142266-62-4 92%
Reaction Conditions:
Stage #1:2,5,6-Trichloronicotinic Acid with 1,1'-carbonyldiimidazole in tetrahydrofuran at 50; for 1.08333 h;Inert atmosphere;
Stage #2: with ammonium hydroxide in toluene at 0 - 20; for 0.166667 h;
Steps:
2,5,6-Trichloronicotinamide
1,1'-Carbonyldiimidazole (40 g, 247 mmol) was added in portions to 2,5,6-trichloronicotinic acid (50.7 g, 224 mmol, Combi-Blocks, San Diego, Calif., USA) in THF (400 mL), allowing gas evolution to cease between additions.
The resulting mixture was stirred for 5 min and then was degassed with house vacuum and flushed with nitrogen (*2).
The resulting mixture was heated to 50° C. for 60 min, then diluted with toluene (100 mL) and concentrated to half volume.
The resulting mixture was cooled to 0° C. and ammonium hydroxide (60 mL, 437 mmol) was added slowly via syringe.
The reaction was stirred for 10 min at room temperature, diluted with EtOAc (200 mL) and washed with water (3*100 mL).
The organic layer was dried over anhydrous sodium sulfate and concentrated.
The residue was suspended in 9:1 heptane/EtOAc (300 mL) and filtered.
The filtered solids were collected and the remaining mother liquor was partially evaporated to half volume, cooled to 0° C., and filtered.
The two crops of filtered solids were combined to provide 2,5,6-trichloronicotinamide (Intermediate P, 46.2 g, 92% yield).
References:
Amgen Inc.;ALLEN, John Gordon;LANMAN, Brian Alan;CHEN, Jian;REED, Anthony B.;CEE, Victor J.;LIU, Longbin;LOPEZ, Patricia;WURZ, Ryan Paul;NGUYEN, Thomas T.;Booker, Shon;ALLEN, Jennifer Rebecca;CHU-MOYER, Margaret;AMEGADZIE, Albert;CHEN, Ning;GOODMAN, Clifford;LOW, Jonathan D.;MA, Vu Van;MINATTI, Ana Elena;NISHIMURA, Nobuko;PICKRELL, Alexander J.;WANG, Hui-Ling;SHIN, Youngsook;SIEGMUND, Aaron C.;YANG, Kevin C.;TAMAYO, Nuria A.;WALTON, Mary;XUE, Qiufen US2019/374542, 2019, A1 Location in patent:Paragraph 0784-0785
58584-88-6
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142266-62-4
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40381-92-8
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52465-59-5
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142266-62-4
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29553-51-3
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142266-62-4
79 suppliers
$121.00/100mg