Methanol → 5-(3,5-dimethylisoxazol-4-yl)-N'-hydroxy-1-(4-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carboximidamide

HRID 242178Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 242178
Cl.[NH2:2][OH:3].C([O-])(O)=O.[Na+].CO.[CH3:11][C:12]1[C:16]([C:17]2[N:21]([C:22]3[CH:27]=[CH:26][C:25]([O:28]C)=[CH:24][CH:23]=3)[N:20]=[C:19]([CH3:30])[C:18]=2[C:31]#[N:32])=[C:15]([CH3:33])[O:14][N:13]=1>O.[Cl-].[Na+].O.CCOC(C)=O>[NH2:13][OH:14].[CH3:11][C:12]1[C:16]([CH:17]2[N:21]([C:22]3[CH:23]=[CH:24][C:25]([OH:28])=[CH:26][CH:27]=3)[N:20]=[C:19]([CH3:30])[CH:18]2[C:31](=[N:2][OH:3])[NH2:32])=[C:15]([CH3:33])[O:14][N:13]=1.[CH3:11][C:12]1[C:16]([C:17]2[N:21]([C:22]3[CH:23]=[CH:24][C:25]([OH:28])=[CH:26][CH:27]=3)[N:20]=[C:19]([CH3:30])[C:18]=2[C:31](=[N:2][OH:3])[NH2:32])=[C:15]([CH3:33])[O:14][N:13]=1

Komponenten

10

Edukt 4

HCID 887MethanolHCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 671200255-(3,5-dimethylisoxazol-4-yl)-1-(4-methoxyphenyl)-3-methyl-1H-pyrazole-4-carbonitrile

Produkt 3

HCID 787HydroxylamineHCID 759521745-(3,5-dimethylisoxazol-4-yl)-N'-hydroxy-1-(4-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carboximidamideAusbeute 62,5 %HCID 866689725-(3,5-dimethylisoxazol-4-yl)-N'-hydroxy-1-(4-hydroxyphenyl)-3-methyl-4H-pyrazole-4-carboximidamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

A hydroxylamine solution was prepared. Hydroxylamine-HCl (26 mg, 0.37 mmol) and NaHCO3 (32 mg, 0.37 mmol) dissolved in water (0.2 mL), methanol (0.4 mL) was stirred 2 min until gas ceased to evolve, the mixture was filtered and degassed (N2). This was added to the 5-(3,5-dimethylisoxazol-4-yl)-1-(4-methoxyphenyl)-3-methyl-1H-pyrazole-4-carbonitrile (11 mg, 0.037 mmol) and stirred at 130° C. for 30 min in the microwave. EtOAc and brine were added and the phases were separated. Purification using preparative HPLC gave E1 5-(3,5-dimethylisoxazol-4-yl)-N′-hydroxy-1-(4-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carboximidamide (2.52 mg, 7.71 μmol, 21%) ES/MS m/z: 328.19 (M+H), 326.22 (M−H); 1H NMR (acetone-d6, 500 MHz): 7.10 m 2H; 6.84 m 2H, 2.36 s 3H, 2.10 s 3H, 1.89 s 3H. Starting material 5-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carbonitrile was recovered (0.99 mg, 3.36 μmol) as well as E2 5-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carboxamide (3.22 mg, 0.01 mmol) ES/MS m/z: 313.17 (M+H), 311.22 (M−H); 1H NMR (acetone-d6, 500 MHz): 7.10 m 2H, 6.85 m 2H, 2.47 s 3H, 2.12 s 3H, 1.95 s 3H. Identification of Example 6 by 1H-NMR showed that the oxime product was a single isomer, but did not confirm whether the (E) or (Z) oxime isomer had been obtained.

Aufarbeitung

  1. filtrationthe mixture was filtered
  2. customdegassed (N2)
  3. customthe phases were separated
  4. customPurification

Quellen und Nachweise

ORD-Eintrag
ord-01aecca03e9545e0b2298dc065d2018b
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08653112B2

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