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Triethylamine → tert-butyl N-[[4-[5-[6-(4-isopropylsulfonylphenyl)pyrazin-2-yl]isoxazol-3-yl]phenyl]methyl]-N-methyl-carbamate

HRID 522533
ノート
印刷プレビュー

反応式

HRID 522533 の反応式
C1C(=O)N(Cl)C(=O)C1.[OH:9][N:10]=[CH:11][C:12]1[CH:27]=[CH:26][C:15]([CH2:16][N:17]([CH3:25])[C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:14][CH:13]=1.[C:28]([C:30]1[CH:35]=[N:34][CH:33]=[C:32]([C:36]2[CH:41]=[CH:40][C:39]([S:42]([CH:45]([CH3:47])[CH3:46])(=[O:44])=[O:43])=[CH:38][CH:37]=2)[N:31]=1)#[CH:29].CCN(CC)CC>CN(C=O)C.CCOC(C)=O.O>[CH:45]([S:42]([C:39]1[CH:38]=[CH:37][C:36]([C:32]2[N:31]=[C:30]([C:28]3[O:9][N:10]=[C:11]([C:12]4[CH:13]=[CH:14][C:15]([CH2:16][N:17]([CH3:25])[C:18](=[O:24])[O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[CH:26][CH:27]=4)[CH:29]=3)[CH:35]=[N:34][CH:33]=2)=[CH:41][CH:40]=1)(=[O:43])=[O:44])([CH3:47])[CH3:46]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 8471TriethylamineHCID 31398ChlorosuccinimideHCID 866651492-Ethynyl-6-(4-(isopropylsulfonyl)phenyl)pyrazineHCID 86690358Tert-butyl 4-((hydroxyimino)methyl)benzyl(methyl)carbamate

生成物 1

HCID 67480464tert-butyl N-[[4-[5-[6-(4-isopropylsulfonylphenyl)pyrazin-2-yl]isoxazol-3-yl]phenyl]methyl]-N-methyl-carbamate

試薬・触媒・溶媒 3

HCID 962Water溶媒
HCID 6228Dimethylformamide溶媒2 回
HCID 8857Ethyl Acetate溶媒

反応条件

温度
65 °C

実験手順

NCS (34.97 mg, 0.2619 mmol) was added to a solution of tert-butyl 4-((hydroxyimino)methyl)benzyl(methyl)carbamate (62.93 mg, 0.2381 mmol) in DMF (1 mL) and the mixture heated at 65° C. for 15 minutes. The reaction mixture was cooled to ambient temperature and 2-ethynyl-6-(4-isopropylsulfonylphenyl)pyrazine (75 mg, 0.2619 mmol) and DMF (2 mL) were added followed by the dropwise addition of Et3N (28.91 mg, 39.82 μL, 0.2857 mmol). The mixture was stirred at ambient temperature for 45 minutes then heated to 65° C. for 1 hour. The mixture was cooled to ambient temperature and diluted with EtOAc and water and the layers separated. The aqueous layer was extracted with EtOAc (×2) and the combined organic extracts washed with water (×3), brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion™, 12 g column, eluting with 0 to 40% EtOAc/Petroleum Ether) to give the sub-title product as a yellow solid. 1H NMR (400.0 MHz, DMSO) d H NMR (400.0 MHz, DMSO) d 9.53 (s, 1H), 9.32 (s, 1H), 8.58 (d, 2H), 8.09 (s, 1H), 8.06 (d, 2H), 8.01 (d, 2H), 7.42 (d, 2H), 4.47 (s, 2H), 3.55 (sept, 1H), 2.82 (s, 3H), 1.46-1.41 (2×s, 9H) and 1.21 (d, 6H) ppm; MS (ES+) 493.2

後処理

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. temperaturethen heated to 65° C. for 1 hour
  3. temperatureThe mixture was cooled to ambient temperature
  4. customthe layers separated
  5. extractionThe aqueous layer was extracted with EtOAc (×2)
  6. washthe combined organic extracts washed with water (×3), brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography (ISCO Companion™, 12 g column, eluting with 0 to 40% EtOAc/Petroleum Ether)

出典と根拠

ORDレコード
ord-d36ce2cc55ad4198831ee623478d2b0c
出典データセット
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09334244B2

反応ノート

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