Toluene → tert-butyl (S)-1-((S)-5-((2-chloro-1-(2-cyanophenyl)-1H-indol-3-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate

HRID 1055457Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1055457
N(C(OCC)=O)=NC(OCC)=O.C1(C)C=CC=CC=1.[CH3:20][N:21]([C@@H:29]([CH3:45])[C:30](=[O:44])[NH:31][C@H:32]1[CH2:38][O:37][C:36]2[CH:39]=[CH:40][CH:41]=[CH:42][C:35]=2[NH:34][C:33]1=[O:43])[C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25].[Cl:46][C:47]1[N:48]([C:58]2[CH:65]=[CH:64][CH:63]=[CH:62][C:59]=2[C:60]#[N:61])[C:49]2[C:54]([C:55]=1[CH2:56]O)=[CH:53][CH:52]=[CH:51][CH:50]=2.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1COCC1.CO>[Cl:46][C:47]1[N:48]([C:58]2[CH:65]=[CH:64][CH:63]=[CH:62][C:59]=2[C:60]#[N:61])[C:49]2[C:54]([C:55]=1[CH2:56][N:34]1[C:33](=[O:43])[C@@H:32]([NH:31][C:30](=[O:44])[C@@H:29]([N:21]([CH3:20])[C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:25])[CH3:26])[CH3:45])[CH2:38][O:37][C:36]3[CH:39]=[CH:40][CH:41]=[CH:42][C:35]1=3)=[CH:53][CH:52]=[CH:51][CH:50]=2

Komponenten

8

Edukt 5

HCID 1140TolueneHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 72713380tert-Butyl methyl((S)-1-oxo-1-((S)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)propan-2-yl)carbamateHCID 900376432-(2-Chloro-3-(hydroxymethyl)-1H-indol-1-yl)benzonitrile

Produkt 1

HCID 131736361tert-butyl (S)-1-((S)-5-((2-chloro-1-(2-cyanophenyl)-1H-indol-3-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamateAusbeute 50 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Diethyl azodicarboxylate solution 40 wt. % in toluene (DEAD 40% w/w, 360 mg, 377 μl, 828 μmol, Eq: 2) was added to a solution of tert-butyl methyl((S)-1-oxo-1-((S)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)propan-2-yl)carbamate (226 mg, 621 μmol, Eq: 1.5), 2-(2-chloro-3-(hydroxymethyl)-1H-indol-1-yl)benzonitrile (117 mg, 414 1=01, Eq: 1.00) and Ph3P (217 mg, 828 μmol, Eq: 2) in THF (5 mL) and the mixture was stirred at RT for 2.5 d. The mixture was diluted with MeOH (10 mL), concentrated and the residue purified by preparative TLC to give tert-butyl (S)-1-((S)-5-((2-chloro-1-(2-cyanophenyl)-1H-indol-3-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (130 mg, 50%) as a yellow solid.

Aufarbeitung

  1. concentrationconcentrated
  2. customthe residue purified by preparative TLC

Quellen und Nachweise

ORD-Eintrag
ord-aa447dff82e14216abea7647dff92d56
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09394263B2

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