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 449813노트

반응식

HRID 449813 반응식
[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

참가 물질

8

반응물 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 34049044-Maleimidobutyric AcidHCID 178484195HCID 178484195, 화합물

생성물 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-methylbutanamide수율 46.2%

시약·촉매·용매 3

HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 22350042dichloromethane N,N-dimethylformamide용매

실험 절차

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.

후처리

  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%)

출처 및 근거

ORD 기록
ord-5c4d6b2c1ba74b0ab336edba394f647b
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08486932B2

반응 노트

불러오는 중…