Ammonium Chloride → 6-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-2-naphthamide

HRID 724224ノート

反応式

HRID 724224 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([C:12]([OH:14])=O)[CH:6]=[CH:5]2.CCCCCC.C([Li])CCC.[CH:26]1[N:30]=[CH:29][N:28]2[CH2:31][CH2:32][C:33](=[O:34])[C:27]=12.[Cl-].[NH4+:36]>C1COCC1.C(OCC)(=O)C>[OH:34][C:33]1([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[CH:8]=[C:7]([C:12]([NH2:36])=[O:14])[CH:6]=[CH:5]3)[C:27]2[N:28]([CH:29]=[N:30][CH:26]=2)[CH2:31][CH2:32]1

参加物

7

反応物 4

HCID 25517Ammonium ChlorideHCID 45498526-Bromo-2-naphthalenecarboxylic acidHCID 111709605,6-Dihydropyrrolo[1,2-c]imidazol-7-oneHCID 178418244HCID 178418244、化合物

生成物 1

HCID 99658856-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-2-naphthamide

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
-100 °C

実験手順

6-Bromo-2-naphthoic acid (1.51 g) was dissolved in dry THF (50 ml) and the mixture was cooled in a liquid nitrogen/diethyl ether bath to −100° C. With stirring the mixture, an n-butyl lithium hexane solution (1.6M; 7.88 ml) was added dropwise at not more than −95° C. over 5 min. The mixture was stirred at −100° C. for 30 min and at −80° C. for 10 min. Thereafter, the mixture was cooled again to −100° C. and a solution of 5,6-dihydro-7H-pyrrolo[1,2-c]imidazol-7-one (0.61 g) in dry THF (11 ml) was added dropwise at not more than −90° C. over 5 min. The mixture was stirred at same temperature for 30 min and warmed to −70° C. over 30 min. A saturated aqueous ammonium chloride solution (25 ml) was added to stop the reaction. After stirring the mixture for 10 min, ethyl acetate (50 ml) was added for partitioning. The organic layer was removed and the aqueous layer was concentrated to dryness. The resulting residue was purified by flash column chromatography and the objective fraction was dissolved in methanol. This solution was concentrated, ether was added to the precipitated powder for filtration and dried to give the title compound (180 mg) as a colorless powder. The mother liquid was concentrated to give a residue (449 mg) containing the title compound.

後処理

  1. stirringThe mixture was stirred at −100° C. for 30 min and at −80° C. for 10 min
  2. temperatureThereafter, the mixture was cooled again to −100° C.
  3. stirringThe mixture was stirred at same temperature for 30 min
  4. temperaturewarmed to −70° C. over 30 min
  5. customthe reaction
  6. stirringAfter stirring the mixture for 10 min
  7. customfor partitioning
  8. customThe organic layer was removed
  9. concentrationthe aqueous layer was concentrated to dryness
  10. customThe resulting residue was purified by flash column chromatography
  11. dissolutionthe objective fraction was dissolved in methanol
  12. concentrationThis solution was concentrated
  13. additionether was added to the precipitated powder for filtration
  14. customdried

出典と根拠

ORDレコード
ord-c4b6bc25174f4413872ba539fd6ac6fe
出典データセット
uspto-grants-2006_11
特許番号
US07141598B2

反応ノート

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