1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (3RS,4RS)-3-(2,4-dichlorophenyl)-N-[(3-hydroxybenzyl)oxy]-2-{(1SR,2SR)-2-[(mesyl)amino]cyclohexyl}-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide

HRID 1747085노트

반응식

HRID 1747085 반응식
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[CH:18]([C:19](O)=[O:20])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](=[O:22])[N:10]1[CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH:24]1[NH:29][S:30]([CH3:33])(=[O:32])=[O:31].O1CCCCC1[O:40][C:41]1[CH:42]=[C:43]([CH:47]=[CH:48][CH:49]=1)[CH2:44][O:45][NH2:46].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>O.C(OCC)(=O)C.CN(C=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[CH:18]([C:19]([NH:46][O:45][CH2:44][C:43]2[CH:47]=[CH:48][CH:49]=[C:41]([OH:40])[CH:42]=2)=[O:20])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](=[O:22])[N:10]1[CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH:24]1[NH:29][S:30]([CH3:33])(=[O:31])=[O:32]

참가 물질

8

반응물 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 59479025O-[3-(tetrahydro-2H-pyran-2-yl oxy)benzyl]hydroxylamineHCID 68445921(3RS,4RS)-3-(2,4-dichlorophenyl)-2-{(1SR,2SR)-2-[(mesyl)amino]cyclohexyl}-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid

생성물 1

HCID 72303598(3RS,4RS)-3-(2,4-dichlorophenyl)-N-[(3-hydroxybenzyl)oxy]-2-{(1SR,2SR)-2-[(mesyl)amino]cyclohexyl}-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide수율 55.6%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To 400 mg of (3RS,4RS)-3-(2,4-dichlorophenyl)-2-{(1SR,2SR)-2-[(mesyl)amino]cyclohexyl}-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid were added 8 ml of DMF, 243 mg of O-[3-(tetrahydro-2H-pyran-2-yl oxy)benzyl]hydroxylamine, 159 mg of HOBt, and 243 mg of WSC, followed by stirring at room temperature for 3 hours. The reaction solution was added with ethyl acetate and water to carry out a liquid separation operation, and the organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then evaporated under reduced pressure. To the residue was added methanol, and concentrated hydrochloric acid was added dropwise thereto under ice-cooling, followed by stirring under ice-cooling for 1 hour. The precipitated crystal was collected by filtration to obtain 275 mg of (3RS,4RS)-3-(2,4-dichlorophenyl)-N-[(3-hydroxybenzyl)oxy]-2-{(1SR,2SR)-2-[(mesyl)amino]cyclohexyl}-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide as a white crystal.

후처리

  1. customa liquid separation operation
  2. washthe organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution
  3. dry with materiala saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate
  4. customevaporated under reduced pressure
  5. additionTo the residue was added methanol, and concentrated hydrochloric acid
  6. additionwas added dropwise
  7. temperatureunder ice-cooling
  8. stirringby stirring under ice-
  9. temperaturecooling for 1 hour
  10. filtrationThe precipitated crystal was collected by filtration

출처 및 근거

ORD 기록
ord-787bc3a56036495c81e5591c5c8bf740
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09150541B2

반응 노트

불러오는 중…