Triethylamine → Tert-butyl 4-(5-(3-amino-6-(4-(isopropylsulfonyl)phenyl)pyrazin-2-yl)-4,5-dihydroisoxazol-3-yl)benzyl(methyl)carbamate

HRID 78692ノート

反応式

HRID 78692 の反応式
C1C(=O)N(Cl)C(=O)C1.[OH:9]/[N:10]=[CH:11]/[C:12]1[CH:17]=[CH:16][C:15]([CH2:18][N:19]([CH3:27])[C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:14][CH:13]=1.[CH:28]([S:31]([C:34]1[CH:39]=[CH:38][C:37]([C:40]2[N:41]=[C:42]([CH:47]=[CH2:48])[C:43]([NH2:46])=[N:44][CH:45]=2)=[CH:36][CH:35]=1)(=[O:33])=[O:32])([CH3:30])[CH3:29].CCN(CC)CC>CN(C=O)C.C(OCC)(=O)C.O>[NH2:46][C:43]1[C:42]([CH:47]2[O:9][N:10]=[C:11]([C:12]3[CH:13]=[CH:14][C:15]([CH2:18][N:19]([CH3:27])[C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[CH:16][CH:17]=3)[CH2:48]2)=[N:41][C:40]([C:37]2[CH:36]=[CH:35][C:34]([S:31]([CH:28]([CH3:29])[CH3:30])(=[O:33])=[O:32])=[CH:39][CH:38]=2)=[CH:45][N:44]=1

参加物

8

反応物 4

HCID 8471TriethylamineHCID 31398ChlorosuccinimideHCID 866827695-(4-(Isopropylsulfonyl)phenyl)-3-vinylpyrazin-2-amineHCID 89484205HCID 89484205、化合物

生成物 1

HCID 86682770Tert-butyl 4-(5-(3-amino-6-(4-(isopropylsulfonyl)phenyl)pyrazin-2-yl)-4,5-dihydroisoxazol-3-yl)benzyl(methyl)carbamate

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
55 °C

実験手順

NCS (75.43 mg, 0.5649 mmol) was added to a solution of tert-butyl N-[[4-[(E)-hydroxyiminomethyl]phenyl]methyl]-N-methyl-carbamate (129.4 mg, 0.4896 mmol) in DMF (571.5 μL) and the reaction mixture heated at 55° C. for 15 min. After the reaction mixture was allowed to cool to room temperature, 5-(4-isopropylsulfonylphenyl)-3-vinyl-pyrazin-2-amine (114.3 mg, 0.3766 mmol) was added followed by the dropwsie addition of Et3N (76.22 mg, 105.0 μL, 0.7532 mmol). The reaction mixture was stirred at rt for 45 mins followed by heating to 65° C. for 1 hour. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (5 mL) and water (5 mL) and the layers separated. The aqueous layer was extracted further with ethyl acetate (2×5 mL) and the combined organic extracts washed with water (3×10 mL), dried over MgSO4, and concentrated in vacuo to a solid. The residue was purified by column chromatography on silica using with 0-100% Ethylacetate/petroleum ether as elaunt to yield tert-butyl 4-(5-(3-amino-6-(4-(isopropylsulfonyl)phenyl)pyrazin-2-yl)-4,5-dihydroisoxazol-3-yl)benzyl(methyl)carbamate. LC/MS m/z 510.1 [M+1-56]+.

後処理

  1. temperatureto cool to room temperature
  2. temperatureby heating to 65° C. for 1 hour
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customthe layers separated
  5. extractionThe aqueous layer was extracted further with ethyl acetate (2×5 mL)
  6. washthe combined organic extracts washed with water (3×10 mL)
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo to a solid
  9. customThe residue was purified by column chromatography on silica using with 0-100% Ethylacetate/petroleum ether as elaunt

出典と根拠

ORDレコード
ord-012ba06a44944f05870b4991cd94a8f4
出典データセット
uspto-grants-2014_09
特許番号
US08841450B2

反応ノート

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