1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-[(R)-3-(2-{4-[1-(2-Ethoxy-ethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepan-1-yl}-ethyl)-3-phenyl-pyrrolidin-1-yl]-1-[5-(3-methanesulfonyl-[1,2,4]triazol-4-yl)-2-methoxy-phenyl]-methanone

HRID 2230747Notes

Reaction equation

HRID 2230747 reaction equation
[CH3:1][S:2]([C:5]1[N:9]([C:10]2[CH:11]=[CH:12][C:13]([O:19][CH3:20])=[C:14]([CH:18]=2)[C:15]([OH:17])=O)[CH:8]=[N:7][N:6]=1)(=[O:4])=[O:3].Cl.Cl.[CH2:23]([O:25][CH2:26][CH2:27][N:28]1[C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=2[N:30]=[C:29]1[N:37]1[CH2:43][CH2:42][CH2:41][N:40]([CH2:44][CH2:45][C@:46]2([C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)[CH2:50][CH2:49][NH:48][CH2:47]2)[CH2:39][CH2:38]1)[CH3:24].O.ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC.C(N(C(C)C)CC)(C)C>ClCCl.CO>[CH2:23]([O:25][CH2:26][CH2:27][N:28]1[C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=2[N:30]=[C:29]1[N:37]1[CH2:43][CH2:42][CH2:41][N:40]([CH2:44][CH2:45][C@:46]2([C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)[CH2:50][CH2:49][N:48]([C:15]([C:14]3[CH:18]=[C:10]([N:9]4[CH:8]=[N:7][N:6]=[C:5]4[S:2]([CH3:1])(=[O:3])=[O:4])[CH:11]=[CH:12][C:13]=3[O:19][CH3:20])=[O:17])[CH2:47]2)[CH2:39][CH2:38]1)[CH3:24]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 184644745-(3-Methanesulfonyl-[1,2,4]triazol-4-yl)-2-methoxy-benzoic acidHCID 701481071-(2-ethoxy-ethyl)-2-{4-[2-((S)-3-phenyl-pyrrolidin-3-yl)-ethyl]-[1,4]diazepan-1-yl}-1H-benzoimidazole dihydrochloride

Product 1

HCID 599022671-[(R)-3-(2-{4-[1-(2-Ethoxy-ethyl)-1H-benzoimidazol-2-yl]-[1,4]diazepan-1-yl}-ethyl)-3-phenyl-pyrrolidin-1-yl]-1-[5-(3-methanesulfonyl-[1,2,4]triazol-4-yl)-2-methoxy-phenyl]-methanoneYield 20.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

Condense 5-(3-methanesulfonyl-[1,2,4]triazol-4-yl)-2-methoxy-benzoic acid (0.125 g, 0.42 mmol) and 1-(2-ethoxy-ethyl)-2-{4-[2-((S)-3-phenyl-pyrrolidin-3-yl)-ethyl]-[1,4]diazepan-1-yl}-1H-benzoimidazole dihydrochloride (0.23 g, 0.42 mmol) in the presence of 1-hydroxybenzotriazole hydrate (0.062 g, 0.51 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (0.97 g, 0.51 mmol), diisopropylethylamine (0.22 mL, 1.26 mmol), and dichloromethane (15 mL) as described for the preparation of Example 124 to afford 0.065 g of the title compound, Rf=0.28 (silica gel, 10% methanol in dichloromethane). The compound may be converted to the dihydrochloride salt by methods well known in the art.

Workup

  1. customas described for the preparation of Example 124

Sources & evidence

ORD record
ord-839a562419514289a2c889ad85fbfcc7
Source dataset
uspto-grants-2002_07
Patent number
US06423704B1

Reaction notes

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