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Hydrochloric Acid → (2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-[5-(hydroxymethyl)pyrazin-2-yl]-3-[(1R)-3-oxocyclopentyl]propanamide

HRID 2192950
ノート
印刷プレビュー

反応式

HRID 2192950 の反応式
[CH:1]1([C:4]2[CH:5]=[C:6]([C@@H:16]([CH2:20][C@H:21]3[CH2:25][CH2:24][C:23](=[O:26])[CH2:22]3)[C:17]([OH:19])=O)[CH:7]=[CH:8][C:9]=2[S:10]([CH:13]2[CH2:15][CH2:14]2)(=[O:12])=[O:11])[CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[Si]([O:40][CH2:41][C:42]1[N:43]=[CH:44][C:45]([NH2:48])=[N:46][CH:47]=1)(C(C)(C)C)(C)C.Cl>ClCCl.O.C1COCC1.N1C=CC=CC=1.CN(C=O)C>[CH:1]1([C:4]2[CH:5]=[C:6]([C@@H:16]([CH2:20][C@H:21]3[CH2:25][CH2:24][C:23](=[O:26])[CH2:22]3)[C:17]([NH:48][C:45]3[CH:44]=[N:43][C:42]([CH2:41][OH:40])=[CH:47][N:46]=3)=[O:19])[CH:7]=[CH:8][C:9]=2[S:10]([CH:13]2[CH2:14][CH2:15]2)(=[O:12])=[O:11])[CH2:3][CH2:2]1
参加物実験手順後処理出典と根拠反応ノート

参加物

10

反応物 4

HCID 313Hydrochloric AcidHCID 65578Oxalyl chlorideHCID 59570882(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanoic acidHCID 595709715-(((tert-Butyldimethylsilyl)oxy)methyl)pyrazin-2-amine

生成物 1

HCID 44198880(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-[5-(hydroxymethyl)pyrazin-2-yl]-3-[(1R)-3-oxocyclopentyl]propanamide
収率 42%

試薬・触媒・溶媒 5

HCID 962Water溶媒2 回HCID 1049Pyridine溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of (2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanoic acid (252 mg) in dichloromethane (2.5 mL) were added oxalyl chloride (68 μL) and DMF (104 μL) under ice-cooling, followed by stirring for 20 minutes. Thereafter, pyridine (65 μL) and 5-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyrazin-2-amine (240 mg) were added thereto under ice-cooling, followed by stirring for 20 minutes under ice-cooling. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated and the obtained residue was purified by silica gel column chromatography (ethyl acetate:chloroform=20:80). Further, it was purified by preparative TLC using the same solvent system to obtain a white amorphous substance (200 mg). A mixture of the obtained amorphous substance, 2 M hydrochloric acid (1 mL), and THF (1 mL) was stirred at room temperature for 2 hours. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated and the obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=50:50) to obtain (2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-[5-(hydroxymethyl)pyrazin-2-yl]-3-[(1R)-3-oxocyclopentyl]propanamide (136 mg) as a white amorphous substance.

後処理

  1. temperaturecooling
  2. temperatureunder ice-cooling
  3. stirringby stirring for 20 minutes under ice-
  4. temperaturecooling
  5. extractionfollowed by extraction with ethyl acetate
  6. washThe organic layer was washed with saturated brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe solvent was evaporated
  9. customthe obtained residue was purified by silica gel column chromatography (ethyl acetate:chloroform=20:80)
  10. customFurther, it was purified by preparative TLC
  11. customto obtain a white amorphous substance (200 mg)
  12. stirringwas stirred at room temperature for 2 hours
  13. extractionfollowed by extraction with ethyl acetate
  14. washThe organic layer was washed with saturated brine
  15. dry with materialdried over anhydrous sodium sulfate
  16. customThe solvent was evaporated
  17. customthe obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=50:50)

出典と根拠

ORDレコード
ord-80e85410e0d347fe94dbbc45a0db4efc
出典データセット
uspto-grants-2012_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08329707B2

反応ノート

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