Triethylamine → N-[2-(3-butoxy-3-o-tolyl-azetidin-1-yl)-1-(4-hydroxybenzyl)-2-oxoethyl]-3-(3H-imidazol-4-yl)propionamide

HRID 540421Notes

Reaction equation

HRID 540421 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]([CH2:68][C:69]1[CH:74]=[CH:73][C:72]([OH:75])=[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].C(=O)([O-])O.[Na+]>CN(C=O)C>[CH2:64]([O:63][C:54]1([C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=2[CH3:62])[CH2:55][N:52]([C:50](=[O:51])[CH:49]([NH:48][C:16](=[O:18])[CH2:9][CH2:10][C:11]2[NH:15][CH:14]=[N:13][CH:12]=2)[CH2:68][C:69]2[CH:74]=[CH:73][C:72]([OH:75])=[CH:71][CH:70]=2)[CH2:53]1)[CH2:65][CH2:66][CH3:67]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 669881952-Amino-1-(3-butoxy-3-o-tolylazetidin-1-yl)-3-(4-hydroxyphenyl)propan-1-one trifluoroacetateHCID 178479756HCID 178479756, compound

Product 1

HCID 46194188N-[2-(3-butoxy-3-o-tolyl-azetidin-1-yl)-1-(4-hydroxybenzyl)-2-oxoethyl]-3-(3H-imidazol-4-yl)propionamideYield 47%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

0.35 ml (2.6 mmol) of triethylamine are added to a solution containing 225 mg (1.3 mmol) of desamino-histidine hydrochloride and 410 mg (1.3 mmol) of TBTU in 5 ml of DMF. After stirring for 1 hour at ambient temperature, 440 mg (0.9 mmol) of 2-amino-1-(3-butoxy-3-o-tolylazetidin-1-yl)-3-(4-hydroxyphenyl)propan-1-one trifluoroacetate are added. After stirring for 72 h at ambient temperature, the reaction medium is treated with a saturated aqueous solution of sodium hydrogen carbonate and then extracted with a 20/80 heptane/ethyl acetate mixture. The organic phase is dried over magnesium sulphate, filtered and concentrated. The product is purified by preparative thin layer chromatography (eluent: 90/10 dichloro-methane/methanol). 205 mg of N-[2-(3-butoxy-3-o-tolyl-azetidin-1-yl)-1-(4-hydroxybenzyl)-2-oxoethyl]-3-(3H-imidazol-4-yl)propionamide are obtained in the form of a white powder with a yield of 47%.

Workup

  1. stirringAfter stirring for 72 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 product is purified by preparative thin layer chromatography (eluent: 90/10 dichloro-methane/methanol)

Sources & evidence

ORD record
ord-f336b85377cd47229563aab7d5871bab
Source dataset
uspto-grants-2014_10
Patent number
US08871187B2

Reaction notes

Loading…