Triethylamine → N-[(R)-2-[3-butoxy-3-(2-fluoro-phenyl)azetidin-1-yl]-1-(4-methoxybenzyl)-2-oxoethyl]-3-(1H-imidazol-4-yl)propionamide

HRID 540409Notes

Reaction equation

HRID 540409 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)CC)C.Cl.[CH2:31]([C:38]([OH:40])=O)[CH2:32][C:33]1[N:37]=[CH:36][NH:35][CH:34]=1.FC(F)(F)C(O)=O.[NH2:48][C@H:49]([CH2:68][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[F:62])[CH2:53]1)=[O:51]>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[F:62])[CH2:53][N:52]([C:50](=[O:51])[C@H:49]([NH:48][C:38](=[O:40])[CH2:31][CH2:32][C:33]2[N:37]=[CH:36][NH:35][CH:34]=2)[CH2:68][C:69]2[CH:74]=[CH:73][C:72]([O:75][CH3:76])=[CH:71][CH:70]=2)[CH2:55]1)[CH2:65][CH2:66][CH3:67]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 66988186(R)-2-amino-1-[3-butoxy-3-(2-fluorophenyl)azetidin-1-yl]-3-(4-methoxy-phenyl)propan-1-one trifluoroacetateHCID 178479756HCID 178479756, compound

Product 1

HCID 178450018N-[(R)-2-[3-butoxy-3-(2-fluoro-phenyl)azetidin-1-yl]-1-(4-methoxybenzyl)-2-oxoethyl]-3-(1H-imidazol-4-yl)propionamideYield 57%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

81 mg (0.3 mmol) of TBTU and 0.1 ml (0.6 mmol) of triethylamine are added to a solution of 42 mg (0.25 mmol) of desamino-histidine hydrochloride in 1 ml of dimethylformamide. After stirring for 10 minutes, 119 mg (0.2 mmol) of (R)-2-amino-1-[3-butoxy-3-(2-fluorophenyl)azetidin-1-yl]-3-(4-methoxyphenyl)propan-1-one trifluoroacetate are added and the reaction medium is stirred for 64 h at ambient temperature. After extraction with a 1/2 heptane/ethyl acetate mixture, the organic phase is washed with 1N aqueous solution of sodium hydroxide and a saturated aqueous solution of sodium chloride, dried over magnesium sulphate, filtered and evaporated. The crude product is purified by silica gel chromatography, elution being carried out with a 90/10 dichloromethane/methanol mixture. 59 mg of N—[(R)-2-[3-butoxy-3-(2-fluoro-phenyl)azetidin-1-yl]-1-(4-methoxybenzyl)-2-oxoethyl]-3-(1H-imidazol-4-yl)propionamide are obtained in the form of a white solid with a yield of 57%.

Workup

  1. stirringthe reaction medium is stirred for 64 h at ambient temperature
  2. extractionAfter extraction with a 1/2 heptane/ethyl acetate mixture
  3. washthe organic phase is washed with 1N aqueous solution of sodium hydroxide
  4. dry with materiala saturated aqueous solution of sodium chloride, dried over magnesium sulphate
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product is purified by silica gel chromatography, elution

Sources & evidence

ORD record
ord-b68e1ff8622b4026b2265dc91f45e35d
Source dataset
uspto-grants-2014_10
Patent number
US08871187B2

Reaction notes

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