Formic Acid → 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonyl-amino]-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]indole-8-carboxylic acid

HRID 715937ノート

反応式

HRID 715937 の反応式
[CH2:1]([N:3]([CH2:34][CH3:35])[CH2:4]/[CH:5]=[CH:6]\[C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[S:14]([NH:17][C:18]1[CH:26]=[CH:25][C:24]2[N:23]3[CH2:27][CH2:28][CH2:29][CH:22]3[CH2:21][C:20]=2[C:19]=1[C:30]([O:32]C)=[O:31])(=[O:16])=[O:15])[CH3:2].O.[OH-].[Li+].C(O)=O>O1CCOCC1.O.CO>[CH2:34]([N:3]([CH2:1][CH3:2])[CH2:4]/[CH:5]=[CH:6]\[C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[S:14]([NH:17][C:18]1[CH:26]=[CH:25][C:24]2[N:23]3[CH2:27][CH2:28][CH2:29][CH:22]3[CH2:21][C:20]=2[C:19]=1[C:30]([OH:32])=[O:31])(=[O:15])=[O:16])[CH3:35]

参加物

7

反応物 3

HCID 284Formic AcidHCID 168937Lithium hydroxide, monohydrateHCID 86712102methyl 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]indole-8-carboxylate2 回

生成物 1

HCID 714724337-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonyl-amino]-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]indole-8-carboxylic acid収率 29.8%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

実験手順

A mixture of methyl 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]indole-8-carboxylate (Intermediate 27, 0.311 g) and lithium hydroxide monohydrate (0.526 g) in dioxane (10 mL) and water (2.5 mL) was irradiated in the microwave at 135° C. for 45 minutes. After cooling, the mixture was diluted with methanol and acidified with formic acid. The mixture was concentrated in vacuo and the residue was diluted with ethanol and toluene and again concentrated in vacuo. The residue was triturated with methanol in DCM (20% solution) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM with a gradient of 0-20%. The resultant solid was triturated with ethyl acetate to give a pale yellow solid which was purified by preparative HPLC (C18), eluting with a mixture of acetonitrile and water, containing 0.1% formic acid with a gradient of 5-70% to give 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonyl-amino]-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]indole-8-carboxylic acid (0.090 g).

後処理

  1. customwas irradiated in the microwave at 135° C. for 45 minutes
  2. temperatureAfter cooling
  3. concentrationThe mixture was concentrated in vacuo
  4. additionthe residue was diluted with ethanol and toluene
  5. concentrationagain concentrated in vacuo
  6. customThe residue was triturated with methanol in DCM (20% solution)
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customthe residue was purified by chromatography on silica
  10. washeluting with a mixture of methanol and DCM with a gradient of 0-20%
  11. customThe resultant solid was triturated with ethyl acetate
  12. customto give a pale yellow solid which
  13. customwas purified by preparative HPLC (C18)
  14. washeluting with a mixture of acetonitrile and water
  15. additioncontaining 0.1% formic acid with a gradient of 5-70%

出典と根拠

ORDレコード
ord-066fd3e131ba4c15aa5de3c5a553b8e1
出典データセット
uspto-grants-2015_11
特許番号
US09187494B2

反応ノート

読み込み中…