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2-Amino-2-thioxoethyl 2,2-dimethylpropanoate → 5-(2-Hydroxymethyl-5-methyl-thiazol-4-yl)-6-methyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2-dihydro-pyridine-3-carboxylic acid 4-methanesulfonyl-benzylamide

HRID 559810
ノート
印刷プレビュー

反応式

HRID 559810 の反応式
Br[CH:2]([CH3:37])[C:3]([C:5]1[CH:6]=[C:7]([C:23]([NH:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([S:33]([CH3:36])(=[O:35])=[O:34])=[CH:29][CH:28]=2)=[O:24])[C:8](=[O:22])[N:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)[C:10]=1[CH3:11])=O.C([O:44][CH2:45][C:46]([NH2:48])=[S:47])(=O)C(C)(C)C>CCO>[CH3:36][S:33]([C:30]1[CH:31]=[CH:32][C:27]([CH2:26][NH:25][C:23]([C:7]2[C:8](=[O:22])[N:9]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:20])([F:19])[F:21])[CH:13]=3)[C:10]([CH3:11])=[C:5]([C:3]3[N:48]=[C:46]([CH2:45][OH:44])[S:47][C:2]=3[CH3:37])[CH:6]=2)=[O:24])=[CH:28][CH:29]=1)(=[O:35])=[O:34]
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

4

反応物 2

HCID 27821132-Amino-2-thioxoethyl 2,2-dimethylpropanoateHCID 866147825-(2-bromopropanoyl)-6-methyl-N-[4-(methylsulfonyl)benzyl]-2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carboxamide

生成物 1

HCID 667254055-(2-Hydroxymethyl-5-methyl-thiazol-4-yl)-6-methyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2-dihydro-pyridine-3-carboxylic acid 4-methanesulfonyl-benzylamide収率 68%

試薬・触媒・溶媒 1

HCID 702
Ethanol
溶媒

反応条件

温度
80 °C

実験手順

5-(2-Bromopropanoyl)-6-methyl-N-[4-(methylsulfonyl)benzyl]-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamide (Example 53 (b), 0.06 g, 0.10 mmol), 2-amino-2-thioxoethyl pivalate (0.022 g, 0.125 mmol), EtOH (2 ml) and a magnetic stirrer bar were placed in a tube designed for microwave synthesis. The vial was sealed and the mixture was heated in a CEM Discover Microwave apparatus (100 W, 80 ° C.) for 40 minutes, giving complete conversion of the starting material to a single product according to LC-MS. The solvents were evaporated to give a crude mixture which was purified on silica giving 0.045 g (76%) of the intermediate pivalyl ester. This compound was dissolved in THF (2 ml) and water (2 ml). To this solution was added NaOH (0.2 mmol, 0.1 ml of a 2M solution), and the mixture was stirred at room temperature overnight. The THF was evaporated off and the water phase was acidified, extracted, and lo the extracts were evaporated. Purification by preparative HPLC gave pure fractions which were freeze-dried to give the title compound (0.040 g, 68%) as a white solid.

後処理

  1. customdesigned for microwave synthesis
  2. customThe vial was sealed
  3. customgiving complete conversion of the starting material to a single product
  4. customThe solvents were evaporated
  5. customto give a crude mixture which
  6. customwas purified on silica giving 0.045 g (76%) of the intermediate pivalyl ester
  7. dissolutionThis compound was dissolved in THF (2 ml)
  8. additionTo this solution was added NaOH (0.2 mmol, 0.1 ml of a 2M solution), and the mixture
  9. customThe THF was evaporated off
  10. extractionextracted
  11. customwere evaporated
  12. customPurification by preparative HPLC
  13. customgave pure fractions which
  14. customwere freeze-dried

出典と根拠

ORDレコード
ord-e4e44774e28b427392508cbdf81ed92a
出典データセット
uspto-grants-2011_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08063073B2

反応ノート

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