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 1055457Notes

Reaction equation

HRID 1055457 reaction equation
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

Participants

8

Reactant 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

Product 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)carbamateYield 50%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  1. concentrationconcentrated
  2. customthe residue purified by preparative TLC

Sources & evidence

ORD record
ord-aa447dff82e14216abea7647dff92d56
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

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