5-Aminoimidazole-4-carboxamide → Temozolomide

HRID 269394

반응식

HRID 269394 반응식
NC1NC=NC=1C(N)=O.[N+:10](=[C:12]1[NH:16][CH2:15][N:14]=[C:13]1[C:17]([NH2:19])=[O:18])=[N-:11].[CH3:20][N:21]=[C:22]=[O:23]>ClCCl>[CH3:20][N:21]1[N:11]=[N:10][C:12]2[N:16]([CH:15]=[N:14][C:13]=2[C:17]([NH2:19])=[O:18])[C:22]1=[O:23]

참가 물질

5

반응물 3

HCID 96795-Aminoimidazole-4-carboxamideHCID 12228Methyl IsocyanateHCID 1363774465-diazo-1H-imidazole-4-carboxamide

생성물 1

HCID 5394Temozolomide

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

In this process, 5-amino-1H-imidazole-4-carboxamide (A) is converted into 5-diazo-1H-imidazole-4-carboxamide (B), which is then cyclized with methylisocyanate in dichloromethane to provide a high yield of clinical-grade Temozolomide. However, this process requires isolation of the unstable and potentially dangerous 5-diazo-1H-imidazole-4-carboxamide (B). Moreover, methylisocyanate is a difficult reagent to handle and ship, especially on the industrial scale, and indeed is better avoided in industrial manufacture. Furthermore, the cycloaddition of methylisocyanate requires a very long reaction time: Table I in J. Med. Chem. 1984, 27, 196-201, suggests 20 days.

출처 및 근거

ORD 기록
ord-956324603b68473d96417d19794af44e
출처 데이터셋
uspto-grants-2008_11
특허 번호
US07446209B2

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