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

HRID 445419노트

반응식

HRID 445419 반응식
[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]

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 516892Sodium Bicarbonate용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-7bf2f65422bc48b985ea1eedfa2407d6
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08476302B2

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