2-methoxyacetic acid [2-[2-[3-(1H-benzimidazol-2-yl)propyl-methylamino]ethyl]-6-fluoro-1-propan-2-yl-3,4-dihydro-1H-naphthalen-2-yl] ester → 2-(3-(methylamino)propyl)-1H-benzimidazole

HRID 2394990Notes

Reaction equation

HRID 2394990 reaction equation
COCC([O:6][C:7]1([CH2:21][CH2:22][N:23]([CH2:25][CH2:26][CH2:27][C:28]2[NH:32][C:31]3[CH:33]=[CH:34][CH:35]=[CH:36][C:30]=3[N:29]=2)[CH3:24])[CH2:16][CH2:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([F:17])[CH:13]=2)[CH:8]1[CH:18]([CH3:20])[CH3:19])=O.[F:37][C:38]1[CH:39]=[C:40]2[C:45](=[CH:46][CH:47]=1)[CH:44]([CH:48]([CH3:50])[CH3:49])[C:43]([CH2:52][C:53]([OH:55])=[O:54])([OH:51])[CH2:42][CH2:41]2>>[F:37][C:38]1[CH:39]=[C:40]2[C:45](=[CH:46][CH:47]=1)[CH:44]([CH:48]([CH3:50])[CH3:49])[C:43]([CH2:52][C:53]([OH:55])=[O:54])([OH:51])[CH2:42][CH2:41]2.[NH:29]1[C:30]2[CH:36]=[CH:35][CH:34]=[CH:33][C:31]=2[N:32]=[C:28]1[CH2:27][CH2:26][CH2:25][NH:23][CH3:22].[NH:29]1[C:30]2[CH:36]=[CH:35][CH:34]=[CH:33][C:31]=2[N:32]=[C:28]1[CH2:27][CH2:26][CH2:25][N:23]([CH3:24])[C:22](=[O:51])[CH2:21][C:7]1([OH:6])[CH2:16][CH2:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([F:17])[CH:13]=2)[CH:8]1[CH:18]([CH3:20])[CH3:19]

Participants

5

Reactant 2

HCID 52302702-methoxyacetic acid [2-[2-[3-(1H-benzimidazol-2-yl)propyl-methylamino]ethyl]-6-fluoro-1-propan-2-yl-3,4-dihydro-1H-naphthalen-2-yl] esterHCID 18974378(6-Fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl)acetic acid

Product 3

HCID 31454002-(3-(methylamino)propyl)-1H-benzimidazoleHCID 10917130HCID 10917130, compoundHCID 18974378(6-Fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl)acetic acid

Procedure

A method of preparing 2-[2-{[3-(1H-benzimidazol-2-yl)propyl]methylamino}ethyl]-6-fluoro-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl methoxyacetate comprises contacting (6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl)acetic acid or an activated derivative of (6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl)acetic acid with [3-(1H-benzimidazol-2-yl)propyl]methylamine to form N-[3-(1H-benzimidazol-2-yl) propyl]-2-(6-fluoro-2-hydroxy-1-isopropyl-1,2,3 ,4-tetrahydronaphthalen-2-yl)-N-methylacetamide, reducing this to 2-[2-{[3-(1H-benzimidazol-2-yl)propyl]methylamino}ethyl]-6-fluoro-1-isopropyl-1, 2,3,4-tetrahydronaphthalen-2-ol, and treating the 2-[2-{[3-(1H-benzimidazol-2-yl) propyl]-methylamino}ethyl]-6-fluoro-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-ol with methoxyacetic acid or an activated derivative of methoxyacetic acid. The invention is particularly applicable to the preparation of 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, and its dihydrochloride salt. N-[3-(1H-benzimidazol-2yl)propyl]-2-(6-fluoro-2-hydroxy-1-isopropyl-1, 2,3,4-tetrahydronaphthalen-2-yl)-N-methylacetamide is new.

Sources & evidence

ORD record
ord-b3836c5eb32c48118c21acb23dc2778b
Source dataset
uspto-grants-1998_09
Patent number
US05811556

Reaction notes

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