Hexamethyldisilazane → Letrozole

HRID 646656

반응식

HRID 646656 반응식
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C[Si](C)(C)N[Si](C)(C)C.[NH2-:20].[Na+].[F:22][C:23]1[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][CH:24]=1.[NH:31]1[CH:35]=[N:34][C:33]([CH2:36][C:37]2[CH:44]=[CH:43][C:40]([C:41]#[N:42])=[CH:39][CH:38]=2)=[N:32]1>O1CCCC1.CC(N(C)C)=O.CN(C)C=O>[NH:31]1[CH:35]=[N:34][C:33]([CH2:36][C:37]2[CH:44]=[CH:43][C:40]([C:41]#[N:42])=[CH:39][CH:38]=2)=[N:32]1.[F:22][C:23]1[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][CH:24]=1.[CH:25]1[C:26]([C:27]#[N:28])=[CH:29][CH:30]=[C:23]([CH:41]([N:42]2[N:32]=[CH:33][N:34]=[CH:35]2)[C:40]2[CH:43]=[CH:44][C:37]([C:36]#[N:20])=[CH:38][CH:39]=2)[CH:24]=1

참가 물질

11

반응물 5

HCID 13838HexamethyldisilazaneHCID 145174-Fluorobenzonitrile2회HCID 24533Sodium amideHCID 2724254Sodium bis(trimethylsilyl)amide2회HCID 178509721HCID 178509721, 화합물

생성물 3

HCID 3902LetrozoleHCID 145174-FluorobenzonitrileHCID 178509721HCID 178509721, 화합물

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매2회HCID 31374Dimethylacetamide용매

실험 절차

Most preferably, the base is sodium bis(trimethylsilyl)amide, which may be prepared from hexamethyldisilazane and sodium amide, or purchased as a 40 percent solution in tetrahydrofuran. To avoid reaction between the 4-fluorobenzonitrile V and the sodium bis(trimethylsilyl)amide, the base is preferably added gradually to the mixture of synthons (all known procedures first generate the anion of intermediate III prior to bringing it into contact with 4-fluorobenzonitrile V). Approximately equimolar amounts of the intermediate III and 4-fluorobenzonitrile V in dimethylacetamide, dimethylformamide, or tetrahydrofuran provide a yield of about 85 percent by weight of pure letrozole after isolation and purification. As no stoichiometric excess of 4-fluorobenzonitrile V is required, any side-reactions with the base are believed to be negligible.

출처 및 근거

ORD 기록
ord-af800d977dea40cdaf93e3d2be94c129
출처 데이터셋
uspto-grants-2010_04
특허 번호
US07705159B2

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