M-Phenylenediamine → (S)-tert-butyl (1-((3-aminophenyl)amino)-1-oxopropan-2-yl)(methyl)carbamate

HRID 2284646Notes

Reaction equation

HRID 2284646 reaction equation
[C:1]([N:8]([CH3:14])[C@H:9]([C:11]([OH:13])=O)[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[C:47]1([NH2:54])[CH:52]=[CH:51][CH:50]=[C:49]([NH2:53])[CH:48]=1.C(=O)([O-])O.[Na+]>CN(C)C=O.C(OCC)(=O)C>[NH2:53][C:49]1[CH:48]=[C:47]([NH:54][C:11](=[O:13])[C@@H:9]([N:8]([CH3:14])[C:1](=[O:2])[O:3][C:4]([CH3:5])([CH3:6])[CH3:7])[CH3:10])[CH:52]=[CH:51][CH:50]=1

Participants

9

Reactant 6

HCID 7935M-PhenylenediamineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acid

Product 1

HCID 90051717(S)-tert-butyl (1-((3-aminophenyl)amino)-1-oxopropan-2-yl)(methyl)carbamateYield 65.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To N-Boc-N-methyl-L-alanine (1.02 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.92 g) and 1-hydroxybenzotriazole monohydrate (1.35 g), N,N-dimethylformamide (15 mL) was added at room temperature, and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture, a solution of N,N-diisopropylethylamine (2.6 mL) and 1,3-phenylenediamine (1.35 g) in N,N-dimethylformamide (4 mL) was added at room temperature, and the mixture was stirred at 40° C. for 3 hours. The reaction mixture was cooled to room temperature, and then saturated aqueous sodium hydrogencarbonate and ethyl acetate were added to the mixture. The organic layer was separated, washed successively with water and saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent, 60 to 25% hexane in ethyl acetate) to obtain amorphous (S)-tert-butyl (1-((3-aminophenyl)amino)-1-oxopropan-2-yl)(methyl)carbamate (B9, 967 mg).

Workup

  1. stirringthe mixture was stirred at 40° C. for 3 hours
  2. customThe organic layer was separated
  3. washwashed successively with water and saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (eluent, 60 to 25% hexane in ethyl acetate)

Sources & evidence

ORD record
ord-3f1028cd0caa441e8cf5e3b7ca14563b
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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