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

HRID 1410127ノート

反応式

HRID 1410127 の反応式
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]([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

参加物

9

反応物 4

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

生成物 2

HCID 787HydroxylamineHCID 759521745-(3,5-dimethylisoxazol-4-yl)-N'-hydroxy-1-(4-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carboximidamide収率 41.7%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
130 °C

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-6f5cb40427fc4351972351c9ed0951d9
出典データセット
uspto-grants-2014_12
特許番号
US08921402B2

反応ノート

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