Triethylamine → tert-butyl (2R,5R)-5-(2-{2-[(benzylsulfonyl)amino]phenyl}ethyl)-2-[2-(2-{[N-(methoxycarbonyl)-beta-phenyl-L-phenylalanyl]amino}phenyl)ethyl]morpholine-4-carboxylate

HRID 629728노트

반응식

HRID 629728 반응식
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][C@H:10]1[N:15]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:14][C@@H:13]([CH2:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[NH:31][C:32](=[O:52])[C@@H:33]([NH:47][C:48]([O:50][CH3:51])=[O:49])[CH:34]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[O:12][CH2:11]1.C(N(CC)CC)C.[C:60]1([CH2:66][S:67](Cl)(=[O:69])=[O:68])[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(OCC)(=O)C>[CH2:66]([S:67]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][C@H:10]1[N:15]([C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])[CH2:14][C@@H:13]([CH2:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[NH:31][C:32](=[O:52])[C@H:33]([CH:34]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[NH:47][C:48]([O:50][CH3:51])=[O:49])[O:12][CH2:11]1)(=[O:69])=[O:68])[C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1

참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 74740Phenylmethanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 86726326tert-Butyl(2R,5R)-5-[2-(2-aminophenyl)ethyl]-2-{2-[2-({(2S)-2-[(methoxycarbonyl)amino]-3,3-diphenylpropanoyl}amino)phenyl]ethyl}morpholine-4-carboxylate

생성물 1

HCID 86726329tert-butyl (2R,5R)-5-(2-{2-[(benzylsulfonyl)amino]phenyl}ethyl)-2-[2-(2-{[N-(methoxycarbonyl)-beta-phenyl-L-phenylalanyl]amino}phenyl)ethyl]morpholine-4-carboxylate

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

To tert-Butyl(2R,5R)-5-[2-(2-aminophenyl)ethyl]-2-{2-[2-({(2S)-2-[(methoxycarbonyl)amino]-3,3-diphenylpropanoyl}amino)phenyl]ethyl}morpholine-4-carboxylate (1.0 equiv) in CH2Cl2 (0.1 M) were added triethylamine (3 eq) and phenylmethanesulfonyl chloride (1.5 eq). The reaction was stirred at room temperature for 18 h and ethyl acetate and saturated sodium bicarbonate were added. Aqueous layer was extracted twice with ethyl acetate and combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified using automated silica-gel flash chromatography using a solvent gradient of 20% to 100% of ethyl acetate and hexanes to afford tert-butyl (2R,5R)-5-(2-{2-[(benzylsulfonyl)amino]phenyl}ethyl)-2-[2-(2-{[N-(methoxycarbonyl)-β-phenyl-L-phenylalanyl]amino}phenyl)ethyl]morpholine-4-carboxylate which was treated with TFA by following procedure described in step 12 of Example 1 to afford the title compound.

후처리

  1. extractionAqueous layer was extracted twice with ethyl acetate
  2. washwere washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified

출처 및 근거

ORD 기록
ord-359ee37cb3de46c494f4334b98ec3059
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09315475B2

반응 노트

불러오는 중…