1,8-Diazabicyclo(5.4.0)undec-7-ene → 4-(2-Chloro-7,7-dioxo-4,7-dihydro-1,7lambda6-dithia-4,6-diaza-inden-5-yl)-5-hydroxy-2-(3-methyl-butyl)-6-thiophen-2-yl-2H-pyridazin-3-one

HRID 30980노트

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HRID 30980 반응식
[Cl:1][C:2]1[S:6][C:5]([S:7](=[O:10])(=[O:9])[NH2:8])=[C:4]([NH:11][C:12]([C:14]2[C:15](=[O:31])[N:16]([CH2:26][CH2:27][CH:28]([CH3:30])[CH3:29])[N:17]=[C:18]([C:21]3[S:22][CH:23]=[CH:24][CH:25]=3)[C:19]=2[OH:20])=O)[CH:3]=1.N12CCCN=C1CCCCC2>N1C=CC=CC=1>[Cl:1][C:2]1[S:6][C:5]2[S:7](=[O:10])(=[O:9])[N:8]=[C:12]([C:14]3[C:15](=[O:31])[N:16]([CH2:26][CH2:27][CH:28]([CH3:30])[CH3:29])[N:17]=[C:18]([C:21]4[S:22][CH:23]=[CH:24][CH:25]=4)[C:19]=3[OH:20])[NH:11][C:4]=2[CH:3]=1

참가 물질

4

반응물 2

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 586938565-Hydroxy-2-(3-methyl-butyl)-3-oxo-6-thiophen-2-yl-2,3-dihydro-pyridazine-4-carboxylic acid (5-chloro-2-sulfamoyl-thiophen-3-yl)-amide

생성물 1

HCID 1361485714-(2-Chloro-7,7-dioxo-4,7-dihydro-1,7lambda6-dithia-4,6-diaza-inden-5-yl)-5-hydroxy-2-(3-methyl-butyl)-6-thiophen-2-yl-2H-pyridazin-3-one수율 15%

시약·촉매·용매 1

HCID 1049Pyridine용매

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온도
140 °C

실험 절차

To a solution of the amide intermediate (15a) (54 mg, 0.11 mmol) in anhydrous pyridine (1.5 mL) in a sealed tube, 1,8-Diazabicyclo[5,4,0] undec-7-ene (DBU) (20 μL) was added and then stirred at 140° C. (oil bath temperature) for 24 hrs. The reaction mixture was cooled to room temperature and solvent was removed in vacuo, and then the residue was further dried in high vacuum for 2 hrs. The crude material was purified by flash chromatography on silica gel using hexane and EtOAc to give the desired product (5m) (8.0 mg, 15%) as a yellow solid. LC-MS (ESI+): m/e=485.21 [M+1]+ (exact ms: 484.01); 1H NMR (400 MHz, DMSO-d6): δ 7.86 (dd, 1H, J=3.2, 1.2 Hz), 7.52 (dd, 1H, J=5.2, 0.8 Hz), 7.46 (s, 1H), 7.07 (dd, 1H, J=5.2, 3.2 Hz), 4.03 (m, 2H), 1.60 (m, 3H), 0.93 (d, 6H, J=6.4 Hz).

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customsolvent was removed in vacuo
  3. customthe residue was further dried in high vacuum for 2 hrs
  4. customThe crude material was purified by flash chromatography on silica gel

출처 및 근거

ORD 기록
ord-a597ca422581475a8f70337ea01573ff
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07425552B2

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