Citric Acid → HCID 178490234, compound

HRID 540390Notes

Reaction equation

HRID 540390 reaction equation
[CH3:1]N(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.[NH:32]1[CH:36]=[C:35]([CH2:37][CH2:38][C:39]([NH:41][C@H:42]([CH2:46][C:47]2[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=2)[C:43]([OH:45])=O)=[O:40])[N:34]=[CH:33]1.[F:55][C:56]([F:61])([F:60])[C:57]([OH:59])=[O:58].[OH:62][C:63]1([C:67]2[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=2)[CH2:66][NH:65][CH2:64]1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)Cl.CN(C=O)C.CN(C=O)C>[F:55][C:56]([F:61])([F:60])[C:57]([OH:59])=[O:58].[OH:62][C:63]1([C:67]2[CH:72]=[CH:71][CH:70]=[CH:69][C:68]=2[CH3:1])[CH2:66][N:65]([C:43](=[O:45])[C@@H:42]([NH:41][C:39](=[O:40])[CH2:38][CH2:37][C:35]2[N:34]=[CH:33][NH:32][CH:36]=2)[CH2:46][C:47]2[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=2)[CH2:64]1

Participants

8

Reactant 5

HCID 311Citric AcidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 669881473-Phenylazetidin-3-ol; trifluoroacetic acidHCID 178490237HCID 178490237, compound

Product 1

HCID 178490234HCID 178490234, compoundYield 10%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

2 ml of DMF, 106 mg (0.33 mmol) of TBTU and 1 ml of DIEA are added to 105 mg (0.33 mmol) of (R)-2-(3-1H-imidazol-4-ylpropionylamino)-3-(4-methoxyphenyl)propanoic acid. The reaction medium is left to stir for 15 minutes at ambient temperature. 36 mg (0.13 mmol) of 3-hydroxy-3-phenylazetidine trifluoroacetate dissolved in 5 ml of a 1/4 DCM/DMF solution are added dropwise and stirred at ambient temperature for 16 hours. A 5% citric acid solution is added, followed by extraction with dichloromethane. The organic phase is washed with a saturated solution of potassium hydrogen carbonate. The organic phase is dried and evaporated to dryness. The crude product obtained is purified by silica gel chromatography (eluent 9/1 dichloromethane/methanol). 6 mg of N—[(S)-2-(3-hydroxy-3-o-tolylazetidin-1-yl)-1-(4-methoxybenzyl)-2-oxoethyl]-3-(1H-imidazol-4-yl)propionamide trifluoroacetate are obtained in the form of a white powder with a yield of 10%.

Workup

  1. waitThe reaction medium is left
  2. additionare added dropwise
  3. stirringstirred at ambient temperature for 16 hours
  4. extractionfollowed by extraction with dichloromethane
  5. washThe organic phase is washed with a saturated solution of potassium hydrogen carbonate
  6. customThe organic phase is dried
  7. customevaporated to dryness
  8. customThe crude product obtained
  9. customis purified by silica gel chromatography (eluent 9/1 dichloromethane/methanol)

Sources & evidence

ORD record
ord-6dfb1bf36ee547d9ad34776beba18edb
Source dataset
uspto-grants-2014_10
Patent number
US08871187B2

Reaction notes

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