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 629728

Reaktionsgleichung

Reaktionsgleichung von HRID 629728
[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

Komponenten

7

Edukt 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

Produkt 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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-359ee37cb3de46c494f4334b98ec3059
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09315475B2

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