(S)-2-((3-(4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)-2-hydroxypropyl)amino)acetic acid ethyl ester → (S)-2-((3-(4-(5-(2-Cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)-2-hydroxypropyl)amino)acetic acid

HRID 2278785Notes

Reaction equation

HRID 2278785 reaction equation
C([O:3][C:4](=[O:39])[CH2:5][NH:6][CH2:7][C@H:8]([OH:38])[CH2:9][O:10][C:11]1[C:16]([CH3:17])=[CH:15][C:14]([C:18]2[N:22]=[C:21]([C:23]3[CH:28]=[C:27]([O:29][CH3:30])[N:26]=[C:25]([CH:31]4[CH2:35][CH2:34][CH2:33][CH2:32]4)[CH:24]=3)[O:20][N:19]=2)=[CH:13][C:12]=1[CH2:36][CH3:37])C>C1COCC1.CO.[Li+].[OH-]>[CH:31]1([C:25]2[CH:24]=[C:23]([C:21]3[O:20][N:19]=[C:18]([C:14]4[CH:15]=[C:16]([CH3:17])[C:11]([O:10][CH2:9][C@@H:8]([OH:38])[CH2:7][NH:6][CH2:5][C:4]([OH:39])=[O:3])=[C:12]([CH2:36][CH3:37])[CH:13]=4)[N:22]=3)[CH:28]=[C:27]([O:29][CH3:30])[N:26]=2)[CH2:32][CH2:33][CH2:34][CH2:35]1

Participants

5

Reactant 1

HCID 70557560(S)-2-((3-(4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)-2-hydroxypropyl)amino)acetic acid ethyl ester

Product 1

HCID 57524452(S)-2-((3-(4-(5-(2-Cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)-2-hydroxypropyl)amino)acetic acidYield 53.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3939Lithium HydroxideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of (S)-2-((3-(4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)-2-hydroxypropyl)amino)acetic acid ethyl ester (60 mg, 0.114 mmol) in THF (3 mL), methanol (3 mL) and 2 N aq. LiOH (1 mL) is stirred at rt for 2 h. The solvent is evaporated and the residue is dissolved in 2 N aq. HCl (10 mL) and extracted four times with DCM (4×20 mL). The org. extracts are combined, dried over MgSO4, filtered and concetrated. The crude product is purified by prep. HPLC to give the title compound (31 mg) as a white solid; LC-MS*: tR=0.86 min, [M+H]+=511.19; 1H NMR (CD3OD): δ 7.88 (s, 1H), 7.86 (s, 1H), 7.54 (s, 1H), 7.30 (s, 1H), 4.30-4.36 (m, 1H), 4.01 (s, 3H), 3.87-3.98 (m, 2H), 3.63 (s, 2H), 3.46 (dd, J1=12.5 Hz, J2=2.9 Hz, 1H), 3.24-3.32 (m, 2H), 2.81 (q, J=7.6 Hz, 2H), 2.42 (s, 3H), 2.07-2.17 (m, 2H), 1.86-1.98 (m, 4H), 1.74-1.82 (m, 2H), 1.32 (t, J=7.6 Hz, 3H).

Workup

  1. customThe solvent is evaporated
  2. dissolutionthe residue is dissolved in 2 N aq. HCl (10 mL)
  3. extractionextracted four times with DCM (4×20 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customThe crude product is purified by prep

Sources & evidence

ORD record
ord-069d6f2f6ae84d1c9488833a7693fc44
Source dataset
uspto-grants-2015_09
Patent number
US09133179B2

Reaction notes

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