1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → Ethyl(2S)-3-(4-{2-[(2,4-difluorobenzyl)(heptyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoate

HRID 854158Notes

Reaction equation

HRID 854158 reaction equation
[CH2:1]([O:3][C@H:4]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:5][C:6]1[CH:16]=[CH:15][C:9]([O:10][CH2:11][C:12]([OH:14])=O)=[CH:8][CH:7]=1)[CH3:2].Cl.[F:23][C:24]1[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:25]=1[CH2:26][NH:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34].Cl.C(N=C=NCCCN(C)C)C>C(Cl)Cl.CN(C1C=CN=CC=1)C>[F:23][C:24]1[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:25]=1[CH2:26][N:27]([CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[C:12](=[O:14])[CH2:11][O:10][C:9]1[CH:8]=[CH:7][C:6]([CH2:5][C@H:4]([O:3][CH2:1][CH3:2])[C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:16][CH:15]=1

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11162260{4-[(2S)-2,3-Diethoxy-3-oxopropyl]phenoxy}acetic AcidHCID 68856873N-(2,4-difluorobenzyl)-N-heptylamine hydrochloride

Product 1

HCID 68857223Ethyl(2S)-3-(4-{2-[(2,4-difluorobenzyl)(heptyl)amino]-2-oxoethoxy}phenyl)-2-ethoxypropanoateYield 36.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of {4-[(2S)-2,3-diethoxy-3-oxopropyl]phenoxy}acetic acid (0.104 g, 0.35 mmol) in methylene chloride (3.5 mL) was added N-(2,4-difluorobenzyl)-N-heptylamine hydrochloride (0.098 g, 0.35 mmol) and DMAP (0.094 g, 0.77 mmol) followed by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.067 g, 0.35 mmol) and the reaction mixture was stirred at room temperature overnight. The mixture was diluted with methylene chloride (50 mL), and the organic phase was washed with 5% HCl (3×25 mL), aqueous NaHCO3 (25 mL) and brine (25 mL), dried over Na2SO4, and concentrated in vacuo. Purification on a prepacked column of silica gel (Isolute® SPE Column, 5 g Si/25 mL) with methanol (0-1% gradient) in methylene chloride as the eluent afforded 0.066 g (36%) of a colourless oil.

Workup

  1. washthe organic phase was washed with 5% HCl (3×25 mL), aqueous NaHCO3 (25 mL) and brine (25 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customPurification on a prepacked column of silica gel (Isolute® SPE Column, 5 g Si/25 mL) with methanol (0-1% gradient) in methylene chloride as the eluent

Sources & evidence

ORD record
ord-86b4f8571c8541d39f02e057b65186cd
Source dataset
uspto-grants-2007_08
Patent number
US07256307B2

Reaction notes

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