反応式
[C:1]([C@@H:3]1[CH2:8][C@H:7]2[C@H:5]([CH2:6]2)[N:4]1[C:9](=[O:30])[C@H:10]([C:19]12[CH2:28][CH:23]3[CH2:24][CH:25]([CH2:27][C:21]([OH:29])([CH2:22]3)[CH2:20]1)[CH2:26]2)[NH:11]C(OC(C)(C)C)=O)#[N:2].[C:31]([O-:39])(=[O:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.[Na+]>>[NH2:11][C@@H:10]([C:19]12[CH2:26][CH:25]3[CH2:24][CH:23]([CH2:22][C:21]([OH:29])([CH2:27]3)[CH2:20]1)[CH2:28]2)[C:9]([N:4]1[C@H:3]([C:1]#[N:2])[CH2:8][C@H:7]2[C@@H:5]1[CH2:6]2)=[O:30].[C:31]([O-:39])(=[O:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1参加物
実験手順
A coupling reaction is then used to couple (αS)-α[[(1,1-dimethylethoxy)carbonyl]amino]-3-hydroxytricyclo[3.3.1.13,7]decane-1-acetic acid, (Formula 3) methanesulfonic acid salt to (1S,3S,5S)-2-azabicyclo[3.1.0]hexane-3-carboxamide (Formula J) in the presence of 1-hydroxybenzotriazole (HOBT) or other known coupling agent to produce 3-(aminocarbonyl)-αS)-α-(3-hydroxytricyclo[3.3.1.13,7]dec-1-yl)-β-oxo-(1S,3S,5S)-2-azabicyclo[3.1.0]hexane-2-ethanecarbamic acid, 1,1-dimethylethyl ester (Formula K). Formula K compound is subjected to dehydration by treating compound K with organic base such as pyridine or triethylamine and trifluoroacetic anhydride, and then subjecting the reaction to hydrolysis by cooling to from about 0 to about 10° C. and adding sodium hydroxide or other strong base such as KOH or LiOH to form Compound L. 3-cyano-(αS)-α-(3-hydroxytricyclo[3.3.1.13,7]dec-1-yl)-β-oxo-(1S,3S,5S)-2-azabicyclo[3.1.0]hexane-2-ethanecarbamic acid, 1,1-dimethylethyl ester (Formula L), which is then deprotected (and treated with sodium benzoate) to form the dipeptidyl peptidase IV inhibitor (1S,3S,5S)-2-[(2S)-2-amino-2-(3-hydroxytricyclo[3.3.1.13,7]dec-1-yl)-1-oxoethyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile, benzoate (1:1) (Formula M).
出典と根拠
- ORDレコード
- ord-7a08a64faefc468dbcb872dd51f524d1
- 出典データセット
- uspto-grants-2010_06
- 特許番号
- US07741082B2
関連ノート
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