Triethylamine → N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-2-(4-hydroxy-3,5-dimethoxyphenyl)acetamide

HRID 658575Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 658575
Cl.[CH3:2][C:3]1[C:7]([CH2:8][N:9]2[CH:13]=[C:12]([NH2:14])[CH:11]=[N:10]2)=[C:6]([CH3:15])[O:5][N:4]=1.[OH:16][C:17]1[C:22]([O:23][CH3:24])=[CH:21][C:20]([CH2:25][C:26](O)=[O:27])=[CH:19][C:18]=1[O:29][CH3:30].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C.Cl>[CH3:2][C:3]1[C:7]([CH2:8][N:9]2[CH:13]=[C:12]([NH:14][C:26](=[O:27])[CH2:25][C:20]3[CH:21]=[C:22]([O:23][CH3:24])[C:17]([OH:16])=[C:18]([O:29][CH3:30])[CH:19]=3)[CH:11]=[N:10]2)=[C:6]([CH3:15])[O:5][N:4]=1

Komponenten

7

Edukt 4

HCID 8471TriethylamineHCID 780934-Hydroxy-3,5-dimethoxyphenylacetic acidHCID 2724699PyBOPHCID 574222641-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-amine hydrochloride

Produkt 1

HCID 57422265N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-2-(4-hydroxy-3,5-dimethoxyphenyl)acetamideAusbeute 29 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 313Hydrochloric AcidLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-amine hydrochloride (Example 4-1a) (376 mg, 1.7 mmol), 2-(4-hydroxy-3,5-dimethoxyphenyl)acetic acid (350 mg, 1.7 mmol), PyBop (1 g, 2 mmol) and triethylamine (605 mg, 6 mmol) were stirred together in DMF (10 mL) at room temperature for 2 hours. The reaction mixture was diluted with aqueous 1N HCl (100 mL) and extracted with DCM (3×, 75 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated on the rotovap. The residue was purified by silica gel chromatography (30% ethyl acetate in hexanes) to afford N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-2-(4-hydroxy-3,5-dimethoxyphenyl)acetamide (189 mg, 29%) as a white solid. 1H NMR (CDCl3, 400 MHz) 2.10 (s, 3H), 2.36 (s, 3H), 3.40 (s, 2H), 3.70 (s, 6H), 5.07 (s, 2H), 6.53 (s, 2H), 7.39 (s, 1H), 7.92 (s, 1H), 8.18 (s, 1H), 10.03 (s, 1H). LC/MS; [M+H] calculated for C19H22N4O5; expected 387.16; found 387.6. Melting point: 187-188° C.

Aufarbeitung

  1. extractionextracted with DCM (3×, 75 mL)
  2. dry with materialThe combined organic extracts were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated on the rotovap
  5. customThe residue was purified by silica gel chromatography (30% ethyl acetate in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-e3b0204e836f4e0db230762a44dc2991
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08076491B2

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