Diisopropylamine → (S)-1-(4-ethylthiazol-2-yl)-2-(4-nitrophenyl)ethanamine

HRID 1842439Notes

Reaction equation

HRID 1842439 reaction equation
C(OC(=O)NC(C(=O)[NH:17][CH:18]([C:29]1[S:30][CH:31]=[C:32]([CH2:34][CH3:35])[N:33]=1)[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=1)CC1C=CC=CC=1)(C)(C)C.Br.C(C1N=C([C@@H](N)CC2C=CC([N+]([O-])=O)=CC=2)SC=1)C.ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC.C(NC(C)C)(C)C>CN(C=O)C.O>[CH2:34]([C:32]1[N:33]=[C:29]([C@@H:18]([NH2:17])[CH2:19][C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=2)[S:30][CH:31]=1)[CH3:35]

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 666949351-(S)-(4-ethylthiazol-2-yl)-2-(4-nitrophenyl)ethyl amine hydrobromideHCID 68698464HCID 68698464, compound

Product 1

HCID 57943187(S)-1-(4-ethylthiazol-2-yl)-2-(4-nitrophenyl)ethanamine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of [2-(4-nitrophenyl)-1-(S)-thiocarbamoylethyl]-carbamic acid tert-butyl ester, 2, (0.245 g, 0.753 mmol), 1-bromo-2-butanone (0.125 g, 0.828 mmol) in CH3CN (5 mL) is refluxed 3 hours. The reaction mixture is cooled to room temperature and diethyl ether is added to the solution and the precipitate which forms is removed by filtration. The solid is dried under vacuum to afford 0.242 g (90% yield) of the desired product. ESI+MS 278 (M+1). Preparation of {1-[1-(4-ethylthiazol-2-yl)-2-(4-nitrophenyl)ethylcarbamoyl]-2-phenylethyl}carbamic acid tert-butyl ester (4): To a solution of 1-(S)-(4-ethylthiazol-2-yl)-2-(4-nitrophenyl)ethyl amine hydrobromide, 3, (0.393 g, 1.1 mmol), (S)-(2-tert-butoxycarbonylamino)-3-phenylpropionic acid (0.220 g, 0.828 mmol) and 1-hydroxybenzotriazole (HOBt) (0.127 g, 0.828 mmol) in DMF (10 mL) at 0° C., is added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI) (0.159 g, 0.828 mmol) followed by diisopropylamine (0.204 g, 1.58 mmol). The mixture is stirred at 0° C. for 30 minutes then at room temperature overnight. The reaction mixture is diluted with water and extracted with EtOAc. The combined organic phase is washed with 1 N aqueous HCl, 5% aqueous NaHCO3, water and brine, and dried over Na2SO4. The solvent is removed in vacuo to afford 0.345 g of the desired product which is used without further purification. LC/MS ESI+525 (M+1).

Workup

  1. customat room temperature
  2. customovernight
  3. extractionextracted with EtOAc
  4. washThe combined organic phase is washed with 1 N aqueous HCl, 5% aqueous NaHCO3, water and brine
  5. dry with materialdried over Na2SO4
  6. customThe solvent is removed in vacuo

Sources & evidence

ORD record
ord-b08689b6f23940388f2a7609e6c3317f
Source dataset
uspto-grants-2015_02
Patent number
US08946232B2

Reaction notes

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