Diisopropylethylamine → {(3E)-4-[(1R)-1-(N-{2-[2-(2-hydroxyethoxy)phenyl]ethyl}-N-methylcarbamoyl)-2-(2-naphthyl)ethylcarbamoyl]-1,1-dimethylbut-3-enyl}carbamic acid tert-butyl ester

HRID 650828노트

반응식

HRID 650828 반응식
[C:1]([O:5][C:6]([NH:8][C:9]([CH3:17])([CH3:16])[CH2:10]/[CH:11]=[CH:12]/[C:13]([OH:15])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[NH2:40][C@H:41]([CH2:58][C:59]1[CH:68]=[CH:67][C:66]2[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=2)[CH:60]=1)[C:42]([N:44]([CH2:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=1[O:54][CH2:55][CH2:56][OH:57])[CH3:45])=[O:43].C(N(C(C)C)C(C)C)C>ClCCl.CN(C)C=O.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]([CH3:17])([CH3:16])[CH2:10]/[CH:11]=[CH:12]/[C:13](=[O:15])[NH:40][C@@H:41]([C:42](=[O:43])[N:44]([CH2:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=1[O:54][CH2:55][CH2:56][OH:57])[CH3:45])[CH2:58][C:59]1[CH:68]=[CH:67][C:66]2[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=2)[CH:60]=1)([CH3:2])([CH3:3])[CH3:4]

참가 물질

9

반응물 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10847814(2E)-5-(tert-Butyloxycarbonylamino)-5-methylhex-2-enoic acidHCID 21310217(2R)-2-amino-N-{2-[2-(2-hydroxyethoxy)phenyl]ethyl}-N-methyl-3-(2-naphthyl)propionamide

생성물 1

HCID 59965088{(3E)-4-[(1R)-1-(N-{2-[2-(2-hydroxyethoxy)phenyl]ethyl}-N-methylcarbamoyl)-2-(2-naphthyl)ethylcarbamoyl]-1,1-dimethylbut-3-enyl}carbamic acid tert-butyl ester수율 61%

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매2회HCID 8857Ethyl Acetate용매

반응 조건

온도
0 °C

실험 절차

(2E)-5-(tert-Butoxycarbonylamino)-5-methylhex-2-enoic acid (95 mg, 0.39 mmol) was dissolved in dichloromethane (1 ml) and N,N-dimethylformamide (1 ml). 1-Hydroxy-7-azabenzotriazole (55 mg, 0,39 mmol) was added. The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (75 mg, 0.39 mmol) was added. The reaction mixture was stirred for 20 min at 0° C. A solution of (2R)-2-amino-N-{2-[2-(2-hydroxyethoxy)pheny]ethyl}-N-methyl-3(2naphthyl)propionamide (155 mg, 0.39 mmol) in dichloromethane (1 ml) and ethyldiisopropylamine (0.07 ml, 0.39 mmol) were added successively. The reaction mixture was stirred for 16 h, while it was warming up to room temperature. It was diluted with ethyl acetate (30 ml) and washed with 10% aqueous sodium hydrogen sulfate solution (30 ml). The aqueous phase was extracted with ethyl acetate (2×20 ml). The combined organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate solution (30 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crued product was purified by flash chromatography on silica (12 g), using ethyl acetate/heptane (2:1) as eluent to give 147 mg of {(3E)-4-[(1R)-1-(N-{2-[2-(2-hydroxyethoxy)phenyl]ethyl}-N-methylcarbamoyl)-2-(2-naphthyl)ethylcarbamoyl]-1,1-dimethylbut-3-enyl}carbamic acid tert-butyl ester.

후처리

  1. stirringThe reaction mixture was stirred for 16 h, while it
  2. temperaturewas warming up to room temperature
  3. washwashed with 10% aqueous sodium hydrogen sulfate solution (30 ml)
  4. extractionThe aqueous phase was extracted with ethyl acetate (2×20 ml)
  5. washThe combined organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate solution (30 ml)
  6. dry with materialdried over magnesium sulfate
  7. customThe solvent was removed in vacuo
  8. customThe crued product was purified by flash chromatography on silica (12 g)

출처 및 근거

ORD 기록
ord-93c143ddc04f494aab7fd9e0db2dd3c1
출처 데이터셋
uspto-grants-2001_08
특허 번호
US06274584B1

반응 노트

불러오는 중…