3-Aminopropionitrile → (S)-Tert-butyl 3-(3'-chlorobiphenyl-4-yl)-1-(2-cyanoethylamino)-1-oxopropan-2-ylcarbamate

HRID 333335Notes

Reaction equation

HRID 333335 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=2)=[CH:16][CH:15]=1)[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN=C=[N:31][CH2:32][CH2:33][CH2:34][N:35](C)C.Cl.C1C=CC2N(O)N=NC=2C=1.NCCC#N>C1COCC1>[Cl:26][C:22]1[CH:21]=[C:20]([C:17]2[CH:18]=[CH:19][C:14]([CH2:13][C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:4])[CH3:3])[C:10]([NH:35][CH2:34][CH2:33][C:32]#[N:31])=[O:11])=[CH:15][CH:16]=2)[CH:25]=[CH:24][CH:23]=1

Participants

6

Reactant 4

HCID 16473-AminopropionitrileHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 58280562(S)-2-(Tert-butoxycarbonylamino)-3-(3'-chlorobiphenyl-4-yl)propanoic acid

Product 1

HCID 68748130(S)-Tert-butyl 3-(3'-chlorobiphenyl-4-yl)-1-(2-cyanoethylamino)-1-oxopropan-2-ylcarbamateYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-2-(tert-butoxycarbonylamino)-3-(3′-chlorobiphenyl-4-yl)propanoic acid (1 g, 2.66 mmol) in THF (30 ml) at room temperature was added EDC.HCl (1.020 g, 5.32 mmol) and HOBT (0.815 g, 5.32 mmol). The reaction was stirred at room temperature for 10 minutes then was added 3-aminopropionitrile (0.389 ml, 5.32 mmol) and TEA (0.742 ml, 5.32 mmol). The reaction mixture was stirred at room temperature for overnight. The reaction mixture was quenched by brine and was extracted with EtOAc. The combined organic layer was washed with brine and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The obtained residue was purified by flash chromatography (silica gel, 2 to 4% EtOH/DCM) and gave the title compound: 1.1 g (yield: 97%). LCMS (condition B): 428.2 (M+1); retention time=1.20 min.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for overnight
  2. customThe reaction mixture was quenched by brine
  3. extractionwas extracted with EtOAc
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe obtained residue was purified by flash chromatography (silica gel, 2 to 4% EtOH/DCM)

Sources & evidence

ORD record
ord-015b635762bf4b78b754266078543213
Source dataset
uspto-grants-2014_11
Patent number
US08877815B2

Reaction notes

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