1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 2-Methyl-2-(4-{[5-(4-trifluoromethoxy-phenyl)-pent-4-ynoylamino]-methyl}-phenoxy)-propionic acid ethyl ester

HRID 852396Notes

Reaction equation

HRID 852396 reaction equation
[CH2:1]([O:3][C:4](=[O:17])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][NH2:16])=[CH:11][CH:10]=1)([CH3:7])[CH3:6])[CH3:2].[F:18][C:19]([F:35])([F:34])[O:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]#[C:28][CH2:29][CH2:30][C:31](O)=[O:32])=[CH:23][CH:22]=1.Cl.CN(C)CCCN=C=NCC.OS([O-])(=O)=O.[K+].CCOCC>ClCCl>[CH2:1]([O:3][C:4](=[O:17])[C:5]([CH3:7])([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:15][NH:16][C:31](=[O:32])[CH2:30][CH2:29][C:28]#[C:27][C:24]2[CH:25]=[CH:26][C:21]([O:20][C:19]([F:34])([F:35])[F:18])=[CH:22][CH:23]=2)=[CH:13][CH:14]=1)[CH3:6])[CH3:2]

Participants

6

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 161091882-(4-Aminomethyl-phenoxy)-2-methyl-propionic acid ethyl esterHCID 68822685HCID 68822685, compoundHCID 86584777KHSO4 ether

Product 1

HCID 694583382-Methyl-2-(4-{[5-(4-trifluoromethoxy-phenyl)-pent-4-ynoylamino]-methyl}-phenoxy)-propionic acid ethyl esterYield 47.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

0.16 g (0.68 mmol) of 2-(4-aminomethyl-phenoxy)-2-methyl-propionic acid ethyl ester [PCT Int. Appl. WO 2002/096895 A1] and 0.16 g (0.62 mmol) of 5-(4-trifluoromethoxy-phenyl)-pent-4-ynoic acid (example 29D]) were dissolved in 4 ml of dichloromethane. This solution was cooled to 0° C. and then 0.14 g (0.74 mmol) of N-(3-dimethylamino-propyl)-N′-ethyl-carbodiimide-hydrochloride was added and the reaction stirred for 28 hours at ambient temperature. It was subsequently poured into aqueous 10% KHSO4/ether and extracted two fold with ether; the organic layers were washed with aqueous saturated NaHCO3, dried (Na2SO4), filtered and evaporated. The crude product was purified by flash chromatography (SiO2; n-heptane/AcOEt=9:1 to 1:2) to give 0.14 g of the title compound as light brown oil.

Workup

  1. extractionextracted two fold with ether
  2. washthe organic layers were washed with aqueous saturated NaHCO3
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude product was purified by flash chromatography (SiO2; n-heptane/AcOEt=9:1 to 1:2)

Sources & evidence

ORD record
ord-658ee856c0c349c88e9b7b01eb04159b
Source dataset
uspto-grants-2007_08
Patent number
US07253192B2

Reaction notes

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