Triethylamine → 3-(2-{2-Ethyl-4-[5-(5-isobutyl-4-methyl-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-ethylamino)-propionic acid

HRID 2037373Notes

Reaction equation

HRID 2037373 reaction equation
Cl.C([O:4][C:5](=[O:9])[CH2:6][CH2:7][NH2:8])C.[CH2:10]([C:12]1[CH:21]=[C:20]([C:22]2[N:26]=[C:25]([C:27]3[CH:32]=[C:31]([CH3:33])[C:30]([CH2:34][CH:35]([CH3:37])[CH3:36])=[CH:29][N:28]=3)[O:24][N:23]=2)[CH:19]=[C:18]([CH3:38])[C:13]=1[O:14][CH2:15][CH2:16]N)[CH3:11].C(N(CC)CC)C>C(O)C>[CH2:10]([C:12]1[CH:21]=[C:20]([C:22]2[N:26]=[C:25]([C:27]3[CH:32]=[C:31]([CH3:33])[C:30]([CH2:34][CH:35]([CH3:36])[CH3:37])=[CH:29][N:28]=3)[O:24][N:23]=2)[CH:19]=[C:18]([CH3:38])[C:13]=1[O:14][CH2:15][CH2:16][NH:8][CH2:7][CH2:6][C:5]([OH:4])=[O:9])[CH3:11]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 442181592-{2-Ethyl-4-[5-(5-isobutyl-4-methyl-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-ethylamine

Product 1

HCID 442181603-(2-{2-Ethyl-4-[5-(5-isobutyl-4-methyl-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-ethylamino)-propionic acidYield 27.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

A solution of β-alanine ethyl ester hydrochloride (88 mg, 570 μmol) in ethanol (2 mL) is filtered over PL-HCO3 MP SPE ion exchange. The methanesulfonic acid ester intermediate of Example 48 (90 mg, 190 μmol) and triethylamine (77 mg, 760 μmol) is added to the filtrate and the mixture is stirred in a sealed vial at 80° C. for 18 h. The mixture is cooled to rt and the solvent is evaporated. The crude 3-(2-{2-ethyl-4-[5-(5-isobutyl-4-methyl-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-ethylamino)-propionic acid ethyl ester is dissolved in ethanol (2 mL) and 1 N aq. NaOH (2 mL) and the mixture is stirred at rt for 3 h. The mixture is neutralised by adding 1 N aq. HCl, the solvent is removed in vacuo and the residue is separated by prep. HPLC to give the title compound (24 mg) as a white solid; LC-MS: tR=0.90 min, [M+H]+=466.79; 1H NMR (CDCl3): δ1.00 (d, J=6.5 Hz, 6H), 1.30 (t, J=7.3 Hz, 3H), 1.90-1.99 (m, 1H), 2.38 (s, 3H), 2.46 (s, 3H), 2.60-2.68 (m, 4H), 2.73 (q, J=7.5 Hz, 2H), 3.20-3.27 (m, 2H), 3.27-3.33 (m, 2H), 4.07-4.15 (m, 2H), 7.92 (s, 1H), 7.94 (s, 1H), 8.08 (s, 1H), 8.54 (s, 1H).

Workup

  1. temperatureThe mixture is cooled to rt
  2. customthe solvent is evaporated
  3. dissolutionThe crude 3-(2-{2-ethyl-4-[5-(5-isobutyl-4-methyl-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-ethylamino)-propionic acid ethyl ester is dissolved in ethanol (2 mL)
  4. stirring1 N aq. NaOH (2 mL) and the mixture is stirred at rt for 3 h
  5. additionby adding 1 N aq. HCl
  6. customthe solvent is removed in vacuo
  7. customthe residue is separated by prep

Sources & evidence

ORD record
ord-df466280e3f74c30876b50f72f440cbf
Source dataset
uspto-grants-2013_11
Patent number
US08575200B2

Reaction notes

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