benzyl (S)-2-((R)-3-((S)-1-(benzofuran-7-yl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamido)-3-cyclopentylpropylmethylcarbamate → (3R)-N-((S)-3-cyclopentyl-1-(methylamino)propan-2-yl)-3-((S)-1-(2,3-dihydrobenzofuran-7-yl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamide

HRID 2355496Notes

Reaction equation

HRID 2355496 reaction equation
[O:1]1[C:5]2[C:6]([C@:10]([C@@H:18]3[CH2:23][CH2:22][CH2:21][N:20]([C:24]([NH:26][C@@H:27]([CH2:41][CH:42]4[CH2:46][CH2:45][CH2:44][CH2:43]4)[CH2:28][N:29](C)[C:30](=O)OCC4C=CC=CC=4)=[O:25])[CH2:19]3)([OH:17])[CH2:11][CH2:12][CH2:13][CH2:14][O:15][CH3:16])=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[CH:2]1>CCOC(C)=O.Cl[Pd]Cl>[CH:42]1([CH2:41][C@H:27]([NH:26][C:24]([N:20]2[CH2:21][CH2:22][CH2:23][C@@H:18]([C@@:10]([C:6]3[C:5]4[O:1][CH2:2][CH2:3][C:4]=4[CH:9]=[CH:8][CH:7]=3)([OH:17])[CH2:11][CH2:12][CH2:13][CH2:14][O:15][CH3:16])[CH2:19]2)=[O:25])[CH2:28][NH:29][CH3:30])[CH2:46][CH2:45][CH2:44][CH2:43]1

Participants

4

Reactant 1

HCID 57544782benzyl (S)-2-((R)-3-((S)-1-(benzofuran-7-yl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamido)-3-cyclopentylpropylmethylcarbamate

Product 1

HCID 57544730(3R)-N-((S)-3-cyclopentyl-1-(methylamino)propan-2-yl)-3-((S)-1-(2,3-dihydrobenzofuran-7-yl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamideYield 46.5%

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of benzyl (S)-2-((R)-3-((S)-1-(benzofuran-7-yl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamido)-3-cyclopentylpropylmethylcarbamate (98.5 mg, 0.156 mmol) in EtOAc (10 mL) was added PdCl2 (30 mg) and the mixture was stirred under a hydrogen balloon at rt for 3˜5 hrs. After filtration, the filtrate was evaporated and the residue, was purified by prep HPLC to afford (3R)—N—((S)-3-cyclopentyl-1-(methylamino)propan-2-yl)-3-((S)-1-(2,3-dihydrobenzofuran-7-yl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamide (36.2 mg, 46.5%). 1H NMR (CD3OD, 400 MHz) δ 0.89 (m, 1H), 1.12-2.15 (m, H), 2.58 (m, 2H), 2.71 (s, 3H), 2.93 (m, 1H), 3.15 (m, 3H), 3.23 (s, 3H), 3.98 (m, 2H), 4.26 (m, 1H), 4.48 (m, 2H), 6.83 (m, 1H), 7.12 (m, 1H), 7.21 (m, 1H).

Workup

  1. filtrationAfter filtration
  2. customthe filtrate was evaporated
  3. customthe residue, was purified by prep HPLC

Sources & evidence

ORD record
ord-9086465f528340cca5b52dfb7c875bc1
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

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