Ethanolamine → 2-(4-(5-(2-Cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)-N-(2-hydroxyethyl)acetamide

HRID 2278786Notes

Reaction equation

HRID 2278786 reaction equation
[CH:1]1([C:6]2[CH:11]=[C:10]([C:12]3[O:16][N:15]=[C:14]([C:17]4[CH:27]=[C:26]([CH3:28])[C:20]([O:21][CH2:22][C:23]([OH:25])=O)=[C:19]([CH2:29][CH3:30])[CH:18]=4)[N:13]=3)[CH:9]=[C:8]([O:31][CH3:32])[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[CH2:55]([CH2:57][NH2:58])[OH:56]>C1COCC1.O.C([O-])(O)=O.[Na+]>[CH:1]1([C:6]2[CH:11]=[C:10]([C:12]3[O:16][N:15]=[C:14]([C:17]4[CH:27]=[C:26]([CH3:28])[C:20]([O:21][CH2:22][C:23]([NH:58][CH2:57][CH2:55][OH:56])=[O:25])=[C:19]([CH2:29][CH3:30])[CH:18]=4)[N:13]=3)[CH:9]=[C:8]([O:31][CH3:32])[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 700EthanolamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 575243792-(4-(5-(2-Cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)acetic acid

Product 1

HCID 575245322-(4-(5-(2-Cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)-N-(2-hydroxyethyl)acetamideYield 25.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 2-(4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)acetic acid (780 mg, 1.65 mmol) in THF (30 mL), HOBt (267 mg, 1.98 mmol) followed by EDC HCl (379 mg, 1.98 mmol) is added. The mixture is stirred at rt for 5 min before ethanolamine (121 mg, 1.98 mmol) is added. Stirring is continued for 3 h. The mixture is diluted with water and sat. aq. NaHCO3 solution and extracted twice with EA. The combined org. extracts are dried over MgSO4, filtered and concentrated. The crude product is purified by prep. HPLC to give the title compound (202 mg) as a colourless oil; LC-MS: tR=1.07 min, [M+H]+=481.01; 1H NMR (CDCl3): δ 7.90 (s, 1H), 7.89 (s, 1H), 7.50 (d, J=0.5 Hz, 1H), 7.35 (t br, J=5.3 Hz, 1H), 7.30 (d, J=0.8 Hz, 1H), 4.39 (s, 2H), 4.02 (s, 3H), 3.87 (t, J=4.9 Hz, 2H), 3.63 (m, 2H), 3.51 (s, 2H), 3.20-3.29 (m, 1H), 2.73 (q, J=7.6 Hz, 2H), 2.38 (s, 3H), 2.06-2.15 (m, 2H), 1.84-1.95 (m, 4H), 1.70-1.80 (m, 2H), 1.33 (t, J=7.6 Hz, 3H).

Workup

  1. additionis added
  2. additionis added
  3. extractionextracted twice with EA
  4. dry with materialextracts are dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product is purified by prep

Sources & evidence

ORD record
ord-4e06637e28be4ea5a0e3938fa8b6412f
Source dataset
uspto-grants-2015_09
Patent number
US09133179B2

Reaction notes

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