Triethylamine → N-[1-(3-butoxy-3-o-tolylazetidine-1-carbonyl)-2-hydroxy-2-(4-methoxy-phenyl)ethyl]-3-(1H-imidazol-4-yl)propionamide

HRID 540426Notes

Reaction equation

HRID 540426 reaction equation
C(N(CC)CC)C.Cl.[CH2:9]([C:16]([OH:18])=O)[CH2:10][C:11]1[N:15]=[CH:14][NH:13][CH:12]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.FC(F)(F)C(O)=O.[NH2:48][CH:49]([CH:68]([OH:77])[C:69]1[CH:74]=[CH:73][C:72]([O:75][CH3:76])=[CH:71][CH:70]=1)[C:50]([N:52]1[CH2:55][C:54]([O:63][CH2:64][CH2:65][CH2:66][CH3:67])([C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=2[CH3:62])[CH2:53]1)=[O:51].[OH-].[Na+]>CN(C)C=O>[CH2:64]([O:63][C:54]1([C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=2[CH3:62])[CH2:53][N:52]([C:50]([CH:49]([NH:48][C:16](=[O:18])[CH2:9][CH2:10][C:11]2[N:15]=[CH:14][NH:13][CH:12]=2)[CH:68]([OH:77])[C:69]2[CH:74]=[CH:73][C:72]([O:75][CH3:76])=[CH:71][CH:70]=2)=[O:51])[CH2:55]1)[CH2:65][CH2:66][CH3:67]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 669881322-Amino-1-(3-butoxy-3-o-tolylazetidin-1-yl)-3-hydroxy-3-(4-methoxyphenyl)propan-1-one trifluoroacetateHCID 178479756HCID 178479756, compound

Product 1

HCID 178450014N-[1-(3-butoxy-3-o-tolylazetidine-1-carbonyl)-2-hydroxy-2-(4-methoxy-phenyl)ethyl]-3-(1H-imidazol-4-yl)propionamideYield 39%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

0.2 ml (1.5 mmol) of triethylamine is added to a solution containing 100 mg (0.6 mmol) of desamino-histidine hydrochloride and 180 mg (0.6 mmol) of TBTU in 5 ml of dimethylformamide. After stirring for 1 h at ambient temperature, 200 mg (0.4 mmol) of 2-amino-1-(3-butoxy-3-o-tolylazetidin-1-yl)-3-hydroxy-3-(4-methoxy-phenyl)propan-1-one trifluoroacetate are added. The reaction medium is stirred for 48 h at ambient temperature and then treated with a 1N aqueous solution of sodium hydroxide and extracted with a 20/80 heptane/ethyl acetate mixture. The organic phase is dried over magnesium sulphate, filtered and concentrated. The residue is purified by preparative thin layer chromatography (eluent: 90/10 dichloromethane/methanol). 80 mg of N-[1-(3-butoxy-3-o-tolylazetidine-1-carbonyl)-2-hydroxy-2-(4-methoxy-phenyl)ethyl]-3-(1H-imidazol-4-yl)propionamide are obtained in the form of a beige powder with a yield of 39%.

Workup

  1. stirringThe reaction medium is stirred for 48 h at ambient temperature
  2. extractionextracted with a 20/80 heptane/ethyl acetate mixture
  3. dry with materialThe organic phase is dried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue is purified by preparative thin layer chromatography (eluent: 90/10 dichloromethane/methanol)

Sources & evidence

ORD record
ord-98d0ba3740504ae6a200be33c71f4bea
Source dataset
uspto-grants-2014_10
Patent number
US08871187B2

Reaction notes

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