Triethylamine → HCID 178490236, compound

HRID 530701Notes

Reaction equation

HRID 530701 reaction equation
F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C.Cl.C[C:32]1[NH:36][CH:35]=[N:34][C:33]=1[CH2:37][CH2:38][C:39]([OH:41])=O.FC(F)(F)C(O)=O.[NH2:49][CH:50]([CH2:77][C:78]1[CH:83]=[CH:82][C:81]([O:84][CH3:85])=[CH:80][CH:79]=1)[C:51]([N:53]1[CH2:56][C:55]([O:64][CH2:65][CH2:66][CH2:67][CH2:68][O:69][CH2:70][C:71]2[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=2)([C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][C:58]=2[CH3:63])[CH2:54]1)=[O:52].[OH-].[Na+]>CN(C)C=O>[CH2:70]([O:69][CH2:68][CH2:67][CH2:66][CH2:65][O:64][C:55]1([C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][C:58]=2[CH3:63])[CH2:54][N:53]([C:51](=[O:52])[C@H:50]([NH:49][C:39](=[O:41])[CH2:38][CH2:37][C:33]2[N:34]=[CH:35][NH:36][CH:32]=2)[CH2:77][C:78]2[CH:79]=[CH:80][C:81]([O:84][CH3:85])=[CH:82][CH:83]=2)[CH2:56]1)[C:71]1[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 669882033-(5-methyl-1H-imidazol-4-yl)propanoic acid hydrochlorideHCID 711521902-Amino-1-[3-(4-benzyloxybutoxy)-3-o-tolylazetidin-1-yl]-3-(4-methoxyphenyl)propan-1-one trifluoroacetate

Product 1

HCID 178490236HCID 178490236, compoundYield 84.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

910 mg (2.83 mmol) of O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate and 0.8 ml (5.67 mmol) of triethylamine are added to a solution of 500 mg (1.89 mmol) of 3-(5-methyl-1H-imidazol-4-yl)propanoic acid hydrochloride in 5 ml of N,N-dimethylformamide. After 60 minutes, 1.4 g (1.89 mmol) of 2-amino-1-[-3-(4-benzyloxybutoxy)-3-o-tolylazetidin-1-yl]-3-(4-methoxyphenyl)propan-1-one trifluoroacetate dissolved in 5 ml of N,N-dimethylformamide are added. The reaction medium is stirred at room temperature for 72 hours, aqueous 1N sodium hydroxide solution is then added and the medium is extracted twice with 50 ml of a 2/8 heptane/ethyl acetate mixture. The organic phase is washed with aqueous 1N sodium hydroxide and then with aqueous 1N hydrochloric acid solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude product obtained is purified by chromatography on silica gel eluted with a 90/10 dichloromethane/methanol mixture. 1 g of N-[(R)-2-[3-(4-benzyloxybutoxy)-3-o-tolylazetidin-1-yl]-1-(4-methoxybenzyl)-2-oxoethyl]-3-(1H-imidazol-4-yl)propionamide is obtained in the form of a white solid, in a yield of 84%.

Workup

  1. additionare added
  2. extractionthe medium is extracted twice with 50 ml of a 2/8 heptane/ethyl acetate mixture
  3. washThe organic phase is washed with aqueous 1N sodium hydroxide
  4. dry with materialwith aqueous 1N hydrochloric acid solution, dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product obtained
  8. customis purified by chromatography on silica gel
  9. washeluted with a 90/10 dichloromethane/methanol mixture

Sources & evidence

ORD record
ord-d35142b3dff346a592d6155881cf1632
Source dataset
uspto-grants-2016_05
Patent number
US09353083B2

Reaction notes

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