Diisopropylethylamine → N-((5-(4-((3-fluorobenzyl)oxy)phenyl)-1,3,4-thiadiazol-2-yl)methyl)-2-hydroxy-8-phenyloctanamide

HRID 445401Notes

Reaction equation

HRID 445401 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[S:17][C:16]([CH2:18][NH2:19])=[N:15][N:14]=2)=[CH:9][CH:8]=1.[OH:23][CH:24]([CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:25](O)=[O:26].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.CCN(C(C)C)C(C)C>CN(C)C=O.C([O-])(O)=O.[Na+]>[F:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[S:17][C:16]([CH2:18][NH:19][C:25](=[O:26])[CH:24]([OH:23])[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)=[N:15][N:14]=2)=[CH:11][CH:12]=1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 537335152-Hydroxy-8-phenyloctanoic acidHCID 66822259(5-(4-((3-Fluorobenzyl)oxy)phenyl)-1,3,4-thiadiazol-2-yl)methanamine

Product 1

HCID 66822711N-((5-(4-((3-fluorobenzyl)oxy)phenyl)-1,3,4-thiadiazol-2-yl)methyl)-2-hydroxy-8-phenyloctanamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A solution of (5-(4-((3-fluorobenzyl)oxy)phenyl)-1,3,4-thiadiazol-2-yl)methanamine (0.85 mmol), 2-hydroxy-8-phenyloctanoic acid (0.85 mmol), 1-hydroxybenzotriazole hydrate (1.0 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.0 mmol), and DIPEA (3.4 mmol) in dimethylformamide (4 mL) was stirred at room temperature for 22 h. The resulting mixture was diluted with NaHCO3 (saturated) and extracted twice with ethyl acetate. The organic phases were combined, washed with brine, dried (Na2SO4) and concentrated. The residue was purified by silica gel chromatography (MeOH—CH2Cl2) to yield N-((5-(4-((3-fluorobenzyl)oxy)phenyl)-1,3,4-thiadiazol-2-yl)methyl)-2-hydroxy-8-phenyloctanamide. A solution of N-((5-(4-((3-fluorobenzyl)oxy)phenyl)-1,3,4-thiadiazol-2-yl)methyl)-2-hydroxy-8-phenyloctanamide (0.22 mmol) in CH2Cl2 (5 mL) was treated with the Dess-Martin periodinane (0.34 mmol) and stirred overnight. The resulting mixture was quenched with a solution of sodium thiosulfate dissolved in saturated aqueous NaHCO3, and the mixture was extracted twice with ethyl acetate. The combined organic extracts were washed with brine, dried (Na2SO4) and concentrated. The residue was purified by chromatography (silica gel, heptane-ethyl acetate) to yield the title compound.

Workup

  1. extractionextracted twice with ethyl acetate
  2. washwashed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography (MeOH—CH2Cl2)

Sources & evidence

ORD record
ord-fe401b0f21dc47f3a6cf69208aab73af
Source dataset
uspto-grants-2013_07
Patent number
US08476302B2

Reaction notes

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