1,2-Dichloroethane → n-(2-(5-(3-(2,4-Dihydroxy-5-isopropylphenyl)-5-hydroxy-4h-1,2,4-triazol-4-yl)-1h-indol-1-yl)ethyl)-4-(2,5-dioxo-2,5-dihydro-1h-pyrrol-1-yl)-n-methylbutanamide

HRID 424902ノート

反応式

HRID 424902 の反応式
[OH:1][C:2]1[N:3]([C:18]2[CH:19]=[C:20]3[C:24](=[CH:25][CH:26]=2)[N:23]([CH2:27][CH2:28][NH:29][CH3:30])[CH:22]=[CH:21]3)[C:4]([C:7]2[CH:12]=[C:11]([CH:13]([CH3:15])[CH3:14])[C:10]([OH:16])=[CH:9][C:8]=2[OH:17])=[N:5][N:6]=1.[O:31]=[C:32]1[CH:36]=[CH:35][C:34](=[O:37])[N:33]1[CH2:38][CH2:39][CH2:40][C:41]([OH:43])=O.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>C(Cl)Cl.CN(C=O)C.O.C(OCC)(=O)C>[OH:17][C:8]1[CH:9]=[C:10]([OH:16])[C:11]([CH:13]([CH3:14])[CH3:15])=[CH:12][C:7]=1[C:4]1[N:3]([C:18]2[CH:19]=[C:20]3[C:24](=[CH:25][CH:26]=2)[N:23]([CH2:27][CH2:28][N:29]([CH3:30])[C:41](=[O:43])[CH2:40][CH2:39][CH2:38][N:33]2[C:34](=[O:37])[CH:35]=[CH:36][C:32]2=[O:31])[CH:22]=[CH:21]3)[C:2]([OH:1])=[N:6][N:5]=1

参加物

8

反応物 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 34049044-Maleimidobutyric AcidHCID 178484195HCID 178484195、化合物

生成物 1

HCID 178438832n-(2-(5-(3-(2,4-Dihydroxy-5-isopropylphenyl)-5-hydroxy-4h-1,2,4-triazol-4-yl)-1h-indol-1-yl)ethyl)-4-(2,5-dioxo-2,5-dihydro-1h-pyrrol-1-yl)-n-methylbutanamide収率 46.2%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 22350042dichloromethane N,N-dimethylformamide溶媒

実験手順

The benzylether [5-(2,4-bis(benzyloxy)-5-isopropylphenyl)-4-(1-(2-(methylamino)ethyl)-1H-indol-5-yl)-4H-1,2,4-triazol-3-ol; 294 mg, 0.5 mmol) was dissolved in 6 ml degassed ethyl acetate and ethanol (1:1). 50 mg Pd/C (10%) was added and the mixture stirred under hydrogen (balloon) at rt for 6 h. After filtration the solvent was removed and the crude purified by chromatography on silica with DCM/MeOH (5-20%)/NH4OH (0.5%) to yield 203 mg (0.5 mmol) 4-(5-hydroxy-4-(1-(2-(methylamino)ethyl)-1H-indol-5-yl)-4H-1,2,4-triazol-3-yl)-6-isopropylbenzene-1,3-diol. This amine (203 mg) was added to 4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)butanoic acid (110 mg, 0.6 mmol), EDC (154 mg, 0.8 mmol) and HOBt (108 mg, 0.8 mmol) in 9 ml DCM/DMF (2:1) at rt. The mixture was stirred for 12 h and then ethyl acetate and water added. The aq. Phase was extracted twice with ethyl acetate and the combined organic extracts washed with brine and dried over MgSO4. The crude was purified by chromatography on silica with DCM/MeOH (0-8%) to yield 133 mg (0.23 mmol) N-(2-(5-(3-(2,4-dihydroxy-5-isopropylphenyl)-5-hydroxy-4H-1,2,4-triazol-4-yl)-1H-indol-1-yl)ethyl)-4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-methylbutanamide.

後処理

  1. extractionThe aq. Phase was extracted twice with ethyl acetate
  2. washthe combined organic extracts washed with brine
  3. dry with materialdried over MgSO4
  4. customThe crude was purified by chromatography on silica with DCM/MeOH (0-8%)

出典と根拠

ORDレコード
ord-f8efb28d6d7143fdb01876a47d46737a
出典データセット
uspto-grants-2012_01
特許番号
US08106083B2

反応ノート

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