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

HRID 242178노트

반응식

HRID 242178 반응식
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

참가 물질

10

반응물 4

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

생성물 3

HCID 787HydroxylamineHCID 759521745-(3,5-dimethylisoxazol-4-yl)-N'-hydroxy-1-(4-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carboximidamide수율 62.5%HCID 866689725-(3,5-dimethylisoxazol-4-yl)-N'-hydroxy-1-(4-hydroxyphenyl)-3-methyl-4H-pyrazole-4-carboximidamide

시약·촉매·용매 3

HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 57417360Sodium chloride; water용매

반응 조건

온도
130 °C

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-01aecca03e9545e0b2298dc065d2018b
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08653112B2

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