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Potassium Carbonate → (S)-7-[(S)-2-(4'-Cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2-oxo-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6-carboxylic acid tert-butyl ester

HRID 602862
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 602862
[C:1]([O:5][C:6]([N:8]1[C@H:17]([C:18](=[O:40])[NH:19][C@H:20]([C:36]([O:38][CH3:39])=[O:37])[CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][C:31]([C:34]#[N:35])=[CH:30][CH:29]=3)=[CH:24][CH:23]=2)[CH2:16][C:15]2[C:10](=[CH:11][C:12]([OH:42])=[C:13]([NH2:41])[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)(O)[O-].[Na+].Cl[CH:49]([C:53]1[CH:58]=[CH:57][C:56]([O:59][CH2:60][C:61]2[CH:66]=[CH:65][C:64]([Cl:67])=[C:63]([Cl:68])[CH:62]=2)=[CH:55][CH:54]=1)[C:50](Cl)=[O:51].C(=O)([O-])[O-].[K+].[K+]>CCOC(C)=O.O>[C:1]([O:5][C:6]([N:8]1[CH:17]([C:18](=[O:40])[NH:19][C@H:20]([C:36]([O:38][CH3:39])=[O:37])[CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:29]=[CH:30][C:31]([C:34]#[N:35])=[CH:32][CH:33]=3)=[CH:24][CH:23]=2)[CH2:16][C:15]2[CH:14]=[C:13]3[C:12]([O:42][C@@H:49]([C:53]4[CH:58]=[CH:57][C:56]([O:59][CH2:60][C:61]5[CH:66]=[CH:65][C:64]([Cl:67])=[C:63]([Cl:68])[CH:62]=5)=[CH:55][CH:54]=4)[C:50](=[O:51])[NH:41]3)=[CH:11][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
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Komponenten

7

Edukt 4

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 593375102-Chloro-2-[4-(3,4-dichloro-benzyloxy)-phenyl]-acetyl chlorideHCID 66922945(S)-6-amino-3-[(S)-2-(4'-cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-7-hydroxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

Produkt 1

HCID 66922703
(S)-7-[(S)-2-(4'-Cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2-oxo-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6-carboxylic acid tert-butyl ester
Ausbeute 61,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel2×

Versuchsvorschrift

(S)-6-amino-3-[(S)-2-(4′-cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-7-hydroxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (1.75 mmol) was dissolved in 5 mL EtOAc, 10 mL water and 15 g sodium bicarbonate added. 2-Chloro-2-[4-(3,4-dichloro-benzyloxy)-phenyl]-acetyl chloride (1.93 mmol) in 5 mL EtOAc was added to the mixture. The resulting mixture stirred at r.t. for 1.5 h. The organic layer was washed with brine, dried over sodium sulfate and concentrated. The resulting residue was dissolved in 5 mL DMF and potassium carbonate (8.75 mmol) added. The reaction stirred at r.t. for 3 h and was poured onto ethyl acetate and water. The organic was dried and concentrated. The residue was purified over silica gel (-hexanes-ethyl acetate) to provide (S)-7-[(S)-2-(4′-Cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2-oxo-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6-carboxylic acid tert-butyl ester (931 mg). LC-MS (m/z) 862.

Aufarbeitung

  1. washThe organic layer was washed with brine
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. dissolutionThe resulting residue was dissolved in 5 mL DMF
  5. stirringThe reaction stirred at r.t. for 3 h
  6. customThe organic was dried
  7. concentrationconcentrated
  8. customThe residue was purified over silica gel (-hexanes-ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-c160e2a3577e4417b261326d03b0ca58
Quelldatensatz
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07906507B2

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