1-Hydroxybenzotriazole → 2-hydroxy-N-((5-(4-hydroxyphenyl)-1,3,4-thiadiazol-2-yl)methyl)-8-phenyloctanamide

HRID 445419Notes

Reaction equation

HRID 445419 reaction equation
[NH2:1][CH2:2][C:3]1[S:7][C:6]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)=[N:5][N:4]=1.[OH:15][CH:16]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:17](O)=[O:18].C1C=CC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=NCC.CCN(C(C)C)C(C)C>CN(C=O)C.C([O-])(O)=O.[Na+]>[OH:15][CH:16]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[C:17]([NH:1][CH2:2][C:3]1[S:7][C:6]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)=[N:5][N:4]=1)=[O:18]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 537335152-Hydroxy-8-phenyloctanoic acidHCID 1363406864-(5-(Aminomethyl)-1,3,4-thiadiazol-2-yl)phenol

Product 1

HCID 1363406892-hydroxy-N-((5-(4-hydroxyphenyl)-1,3,4-thiadiazol-2-yl)methyl)-8-phenyloctanamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A solution of 4-(5-(aminomethyl)-1,3,4-thiadiazol-2-yl)phenol (1.74 mmol), 2-hydroxy-8-phenyloctanoic acid (1.74 mmol), HOBt (2.1 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (2.1 mmol) and DIPEA (6.94 mmol) in DMF (4 mL) was stirred at room temperature overnight. The resulting mixture was diluted with NaHCO3 (saturated) and extracted twice with ethyl acetate. The combined extracts were washed with brine, dried (Na2SO4) and concentrated. The resulting residue was purified by chromatography (silica gel, methanol-CH2Cl2) to yield 2-hydroxy-N-((5-(4-hydroxyphenyl)-1,3,4-thiadiazol-2-yl)methyl)-8-phenyloctanamide. A solution of 2-hydroxy-N-((5-(4-hydroxyphenyl)-1,3,4-thiadiazol-2-yl)methyl)-8-phenyloctanamide (0.18 mmol), 4-bromomethypyridine hydrochloride (0.26 mmol), and potassium carbonate (0.53 mmol) in DMF (4 mL) was stirred at room temperature overnight. The resulting mixture was diluted with ethyl acetate, washed with brine, dried (Na2SO4) and concentrated to yield 2-hydroxy-8-phenyl-N-((5-(4-(pyridin-4-ylmethoxy)phenyl)-1,3,4-thiadiazol-2-yl)methyl)octanamide, which was used in the next step without purification. To a solution of 2-hydroxy-8-phenyl-N-((5-(4-(pyridin-4-ylmethoxy)phenyl)-1,3,4-thiadiazol-2-yl)methyl)octanamide (0.16 mmol) in CH2Cl2 (5 mL) was added the Dess-Martin periodinane (0.23 mmol). The resulting mixture was stirred overnight, then quenched with an excess of a solution of sodium thiosulfate in saturated NaHCO3 (aqueous). The mixture was then extracted twice with ethyl acetate and the combined extracts were washed with brine, dried (Na2SO4) and concentrated. The resulting residue was purified by chromatography (silica gel, heptane-ethyl acetate) to yield the title compound.

Workup

  1. extractionextracted twice with ethyl acetate
  2. washThe combined extracts were washed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe resulting residue was purified by chromatography (silica gel, methanol-CH2Cl2)

Sources & evidence

ORD record
ord-7bf2f65422bc48b985ea1eedfa2407d6
Source dataset
uspto-grants-2013_07
Patent number
US08476302B2

Reaction notes

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