Mibefradil dihydrochloride → HCID 9830209、化合物
反応式
[Ca].[CH3:2][CH:3]([C@@H:5]1[C@@:14]([O:31]C(COC)=O)([CH2:15][CH2:16][N:17]([CH2:19][CH2:20][CH2:21][C:22]2[NH:23][C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][C:29]=3[N:30]=2)[CH3:18])[CH2:13][CH2:12][C:11]2[CH:10]=[C:9]([F:37])[CH:8]=[CH:7][C:6]1=2)[CH3:4].C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl.CC([C@@H]1[C@@](OC(COC)=O)(CCN(CCCC2NC3C=CC=CC=3N=2)C)CCC2C=C(F)C=CC1=2)C.Cl.Cl.FC1C=C2C(=CC=1)[C@H](C(C)C)[C@](CCOS(C1C=CC(C)=CC=1)(=O)=O)(O)CC2.N1C2C=CC=CC=2N=C1CCCNC.CCN(C(C)C)C(C)C>>[NH:23]1[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:29]=2[N:30]=[C:22]1[CH2:21][CH2:20][CH2:19][N:17]([CH3:18])[CH2:16][CH2:15][C@@:14]1([OH:31])[CH2:13][CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:37])[CH:10]=2)[C@@H:5]1[CH:3]([CH3:2])[CH3:4]参加物
実験手順
U.S. Pat. No. 4,808,605 (to Hoffmann-La Roche) discloses various calcium antagonists including mibefradil, (1S,2S)-2-[2-{[3-(1H-benzimidazol-2-yl)propyl]methylamino}ethyl]-6-fluoro-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl methoxyacetate, the dihydrochloride salt of which is the antihypertensive POSICOR®. The synthesis of mibefradil, as described in that patent, involves the reaction of (1S,2S)-6-fluoro-1-isopropyl-2-[2-(4-toluenesulfonyloxy)ethyl]-1, 2,3,4-tetrahydronaphthalene-2-ol with [3-(1H-benzimidazol-2-yl)propyl]methylamine in the presence of Hunig base (ethyldiisopropylamine) to form (1S,2S)-2-[2-{[3-(1H-benzimidazol-2-yl)-propyl]methylamino}ethyl]-6-fluoro-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-ol, which is then acylated with methoxyacetyl chloride to form mibefradil.
出典と根拠
- ORDレコード
- ord-458a637f305a41d791d860595f7878d2
- 出典データセット
- uspto-grants-1998_09
- 特許番号
- US05811556
反応ノート
読み込み中…