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

HRID 1055462Notes

Reaction equation

HRID 1055462 reaction equation
[Cl:1]N1C(=O)CCC1=O.[CH2:9]([N:11]1[C:19]2[C:14](=[C:15]([CH2:20][N:21]3[C:27](=[O:28])[C@@H:26]([NH:29][C:30](=[O:42])[C@@H:31]([N:33]([CH3:41])[C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH3:32])[CH2:25][O:24][C:23]4[CH:43]=[CH:44][CH:45]=[CH:46][C:22]3=4)[CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12]1)[CH3:10]>CN(C=O)C.C([O-])(O)=O.[Na+]>[Cl:1][C:13]1[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][C:15]=2[CH2:20][N:21]2[C:27](=[O:28])[C@@H:26]([NH:29][C:30](=[O:42])[C@@H:31]([N:33]([CH3:41])[C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH3:32])[CH2:25][O:24][C:23]3[CH:43]=[CH:44][CH:45]=[CH:46][C:22]2=3)[N:11]([CH2:9][CH3:10])[CH:12]=1

Participants

5

Reactant 2

HCID 31398ChlorosuccinimideHCID 131736363tert-butyl (S)-1-((S)-5-((1-ethyl-1H-indol-4-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate

Product 1

HCID 131736364tert-butyl (S)-1-((S)-5-((3-chloro-1-ethyl-1H-indol-4-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamateYield 91%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

A solution of N-chlorosuccinimide (NCS, 17.2 mg, 129 μmol, Eq: 1.00) in DMF (2 mL) was added dropwise to a solution of tert-butyl (S)-1-((S)-5-((1-ethyl-1H-indol-4-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (67 mg, 129 μmol, Eq: 1.00) in DMF (12 mL) at 0° C. After 2 h at 0° C. the mixture was diluted with sat. NaHCO3 and extracted with EtOAc. The combined extracts were washed with H2O, concentrated and the residue was purified by preparative TLC to give tert-butyl (S)-1-((S)-5-((3-chloro-1-ethyl-1H-indol-4-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (65 mg, 91%).

Workup

  1. extractionextracted with EtOAc
  2. washThe combined extracts were washed with H2O
  3. concentrationconcentrated
  4. customthe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-ebd20a0a86a340558f77b2850abb050d
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

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