반응 #799490

반응 방정식

Ethyl 1-(5-(7-bromo-2-(3-ethylureido)benzo[d]thiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate

sodium azide

→

crude product

수율 92.3%

Ethyl 1-(5-(7-amino-2-(3-ethylureido)benzo[d]thiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate

수율 92.3%

용매

DMSO water

반응 조건

후처리

1. 1
   기타had been degassed with N2
2. 2
   기타the tube purged with N2
3. 3
   기타sealed
4. 4
   workup.ADDITIONAdditional equivalents of all reagents were added
5. 5
   온도the reaction was heated to 110° C. for a further 2 h
6. 6
   기타The solvents were removed under reduced pressure
7. 7
   기타the resulting residue was triturated with water
8. 8
   기타The resulting solid was isolated by filtration
9. 9
   기타dried

실험 절차

Ethyl 1-(5-(7-bromo-2-(3-ethylureido)benzo[d]thiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate (306 mg, 0.56 mmol), trans-(1R,2R)—N,N′-bismethyl-1,2-cyclohexane (24 mg, 0.17 mmol), sodium azide (73 mg, 1.12 mmol) and sodium ascorbate (6 mg, 0.028 mmol) were stirred in DMSO-water 1:1 (3 ml) which had been degassed with N2. CuI (1.1 mg, 0.0056 mmol) was added and the tube purged with N2, sealed and heated to 110° C. for 2 h. The mixture turned black and evolution of gas was observed. LCMS after this time indicated 34% conversion to the desired amine and starting material remaining. Additional equivalents of all reagents were added and the reaction was heated to 110° C. for a further 2 h. LCMS after this time indicated 75% conversion to the desired material. The solvents were removed under reduced pressure and the resulting residue was triturated with water. The resulting solid was isolated by filtration and dried to afford the crude product (250 mg, 73% purity by LCMS) (92%). This material was used directly in the next step without further purification.

출처