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

HRID 540417Notes

Reaction equation

HRID 540417 reaction equation
C(N(CC)CC)C.[CH2:8]([C:15]([OH:17])=O)[CH2:9][C:10]1[N:14]=[CH:13][NH:12][CH:11]=1.CN(C([O:25]N1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[F:40][C:41]([F:46])([F:45])[C:42]([OH:44])=[O:43].[NH2:47][CH:48]([CH2:67][C:68]1[CH:73]=[CH:72][C:71]([O:74][CH3:75])=[C:70](O)[CH:69]=1)[C:49]([N:51]1[CH2:54][C:53]([O:62][CH2:63][CH2:64][CH2:65][CH3:66])([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][C:56]=2[CH3:61])[CH2:52]1)=[O:50].C(=O)([O-])O.[Na+]>CN(C)C=O>[F:40][C:41]([F:46])([F:45])[C:42]([OH:44])=[O:43].[CH2:63]([O:62][C:53]1([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][C:56]=2[CH3:61])[CH2:52][N:51]([C:49](=[O:50])[CH:48]([NH:47][C:15](=[O:17])[CH2:8][CH2:9][C:10]2[NH:14][CH:13]=[N:12][CH:11]=2)[CH2:67][C:68]2[CH:73]=[CH:72][C:71]([O:74][CH3:75])=[CH:70][C:69]=2[OH:25])[CH2:54]1)[CH2:64][CH2:65][CH3:66]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 669881992-Amino-1-(3-butoxy-3-o-tolylazetidin-1-yl)-3-(3-hydroxy-4-methoxyphenyl)propan-1-one trifluoroacetateHCID 178525356HCID 178525356, compound

Product 1

HCID 66988307N-[2-(3-butoxy-3-o-tolyl-azetidin-1-yl)-1-(2-hydroxy-4-methoxybenzyl)-2-oxoethyl]-3-(3H-imidazol-4-yl)propionamide trifluoro-acetateYield 11.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

0.25 ml (0.6 mmol) of triethylamine is added to a solution of 90 mg (0.6 mmol) of desamino-histidine and 207 mg (0.6 mmol) of TBTU in 2 ml of dimethylformamide. After stirring for 1 h at ambient temperature, 250 mg (0.4 mmol) of 2-amino-1-(3-butoxy-3-o-tolylazetidin-1-yl)-3-(3-hydroxy-4-methoxyphenyl)propan-1-one trifluoroacetate are added and the mixture is stirred for 72 h at ambient temperature. 10 ml of a saturated aqueous solution of sodium hydrogen carbonate are then poured into the reaction medium, which is 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). 30 mg of N-[2-(3-butoxy-3-o-tolyl-azetidin-1-yl)-1-(2-hydroxy-4-methoxybenzyl)-2-oxoethyl]-3-(3H-imidazol-4-yl)propionamide trifluoro-acetate are obtained in the form of a beige powder with a yield of 11%.

Workup

  1. stirringthe mixture is stirred for 72 h at ambient temperature
  2. extractionis extracted 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-6b370a92c7be4fc18bbce35b5af99857
Source dataset
uspto-grants-2014_10
Patent number
US08871187B2

Reaction notes

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