Potassium Iodide → 4'-{5-[(2-Hydroxy-1-hydroxymethyl-ethylamino)-methyl]-[1,3,4]oxadiazol-2-yl}-6-methyl-biphenyl-3-carboxylic acid cyclopropylamide

HRID 31446

Reaktionsgleichung

Reaktionsgleichung von HRID 31446
Cl[CH2:2][C:3]1[O:4][C:5]([C:8]2[CH:13]=[CH:12][C:11](I)=[CH:10][CH:9]=2)=[N:6][N:7]=1.[NH2:15][CH:16]([CH2:19][OH:20])[CH2:17][OH:18].[I-].[K+].[CH:23]1([NH:26][C:27](=[O:44])[C:28]2[CH:33]=[CH:32][C:31]([CH3:34])=[C:30](B3OC(C)(C)C(C)(C)O3)[CH:29]=2)[CH2:25][CH2:24]1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:23]1([NH:26][C:27]([C:28]2[CH:33]=[C:32]([C:11]3[CH:12]=[CH:13][C:8]([C:5]4[O:4][C:3]([CH2:2][NH:15][CH:16]([CH2:19][OH:20])[CH2:17][OH:18])=[N:7][N:6]=4)=[CH:9][CH:10]=3)[C:31]([CH3:34])=[CH:30][CH:29]=2)=[O:44])[CH2:24][CH2:25]1

Komponenten

8

Edukt 5

HCID 4875Potassium IodideHCID 10340Sodium CarbonateHCID 68294SerinolHCID 70910682-(Chloromethyl)-5-(4-iodophenyl)-1,3,4-oxadiazole2×HCID 21914577N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide2×

Produkt 1

HCID 100708654'-{5-[(2-Hydroxy-1-hydroxymethyl-ethylamino)-methyl]-[1,3,4]oxadiazol-2-yl}-6-methyl-biphenyl-3-carboxylic acid cyclopropylamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
20 °C

Versuchsvorschrift

2-Chloromethyl-5-(4-iodophenyl)-[1,3,4]oxadiazole (Intermediate 7) (48 mg, 0.15 mmol), serinol (206 mg, 2.25 mmol) and potassium iodide (25 mg, 0.15 mmol) were dissolved in dimethylformamide (1 ml) and stirred for 18 hours at 20° C. The reaction was evaporated to dryness in vacuo and the product was flushed through a 10 g silica SPE cartridge, eluting with 95:5 ethyl acetate:methanol, to remove inorganic material. Without further purification the crude product was dissolved in 1,2 dimethoxyethane (4 ml). Tetrakis(triphenylphosphine)palladium(0) (16 mg, 0.014 mmol), N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide (Intermediate 17) (0.15 mmol) and 1M aqueous sodium carbonate (0.15 ml, 0.15 mmol) were added. The reaction was heated under nitrogen at 80° C. for 18 hours. Solvent was removed in vacuo and the residue was purified by mass-directed HPLC to yield the desired product.

Aufarbeitung

  1. customThe reaction was evaporated to dryness in vacuo
  2. customthe product was flushed through a 10 g silica SPE cartridge
  3. washeluting with 95:5 ethyl acetate
  4. custommethanol, to remove inorganic material
  5. customWithout further purification the crude product
  6. dissolutionwas dissolved in 1,2 dimethoxyethane (4 ml)
  7. temperatureThe reaction was heated under nitrogen at 80° C. for 18 hours
  8. customSolvent was removed in vacuo
  9. customthe residue was purified by mass-directed HPLC

Quellen und Nachweise

ORD-Eintrag
ord-ada3c6ed74304513bd5f7a6122521efc
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07425555B2

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