Diisopropylethylamine → (S)-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-2-phenyl-acetyl}-2,3-dihydro-1H-indole-2-carboxylic acid ethyl ester

HRID 1477162Notes

Reaction equation

HRID 1477162 reaction equation
[C:1]([O:5][C:6]([N:8]([CH3:14])[C@@H:9]([CH3:13])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[CH2:40]([O:42][C:43]([C@@H:45]1[CH2:53][C:52]2[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=2)[N:46]1[C:54](=[O:63])[C@@H:55]([NH2:62])[C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)=[O:44])[CH3:41].C(N(C(C)C)CC)(C)C>C(Cl)Cl>[CH2:40]([O:42][C:43]([C@@H:45]1[CH2:53][C:52]2[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=2)[N:46]1[C:54](=[O:63])[C@@H:55]([NH:62][C:10](=[O:12])[C@@H:9]([N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH3:14])[CH3:13])[C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)=[O:44])[CH3:41]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 117871727(S)-1-((S)-2-amino-2-phenyl-acetyl)-2,3-dihydro-1H-indole-2-carboxylic acid ethyl ester hydrochloride

Product 1

HCID 117871692(S)-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-2-phenyl-acetyl}-2,3-dihydro-1H-indole-2-carboxylic acid ethyl esterYield 90.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 50 mL round-bottomed flask, (S)-2-(tert-butoxycarbonyl(methyl)amino)propanoic acid (1.52 g, 7.48 mmol, Eq: 1.5) and HATU (1.9 g, 5 mmol, Eq: 1) were combined with DCM (20 mL) to give a light yellow suspension. (S)-1-((S)-2-amino-2-phenyl-acetyl)-2,3-dihydro-1H-indole-2-carboxylic acid ethyl ester hydrochloride (1.8 g, 5 mmol, Eq: 1) was added and followed by diisopropylethylamine (7 mL, 40 mmol, Eq: 8). The reaction was stirred at rt overnight. The crude reaction mixture was concentrated in vacuo, and then dissolved in EtOAc (75 mL). The solution was washed with water and brine, dried and concentrated in vacuo. The crude material was purified by flash chromatography (10% to 30% EtOAc in hexanes) to afford (S)-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-2-phenyl-acetyl}-2,3-dihydro-1H-indole-2-carboxylic acid ethyl ester (2.3 g) as a white foam, m/z=510 (M+H).

Workup

  1. customto give a light yellow suspension
  2. customThe crude reaction mixture
  3. concentrationwas concentrated in vacuo
  4. dissolutiondissolved in EtOAc (75 mL)
  5. washThe solution was washed with water and brine
  6. customdried
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by flash chromatography (10% to 30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-9e48484c13514dd5aa8c058e93139697
Source dataset
uspto-grants-2016_08
Patent number
US09403768B2

Reaction notes

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