Potassium Bicarbonate → HCID 178490238, compound

HRID 540374Notes

Reaction equation

HRID 540374 reaction equation
ClCCl.F[C:5](F)(F)[C:6]([OH:8])=O.C([NH:19][C@@H:20]([CH2:37][C:38]1[N:39]=[CH:40][NH:41][CH:42]=1)[C:21]([NH:23][C@@H:24]([CH2:28][C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=1)[C:25]([OH:27])=O)=[O:22])(=O)C1C=CC=CC=1.CN(C(ON1N=N[C:53]2[CH:54]=C[CH:56]=[CH:57][C:52]1=2)=[N+](C)C)C.[B-](F)(F)(F)F.FC(F)(F)C(O)=O.[CH:72]1([C:78]2([OH:82])[CH2:81][NH:80][CH2:79]2)[CH2:77][CH2:76][CH2:75][CH2:74][CH2:73]1.C(=O)([O-])O.[K+]>CN(C=O)C.CCN(C(C)C)C(C)C.C(Cl)Cl>[CH:72]1([C:78]2([OH:82])[CH2:81][N:80]([C:25](=[O:27])[C@@H:24]([NH:23][C:21]([C@@H:20]([NH:19][C:6](=[O:8])[C:5]3[CH:56]=[CH:57][CH:52]=[CH:53][CH:54]=3)[CH2:37][C:38]3[N:39]=[CH:40][NH:41][CH:42]=3)=[O:22])[CH2:28][C:29]3[CH:30]=[CH:31][C:32]([O:35][CH3:36])=[CH:33][CH:34]=3)[CH2:79]2)[CH2:73][CH2:74][CH2:75][CH2:76][CH2:77]1

Participants

9

Reactant 5

HCID 516893Potassium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 21863450Trifluoroacetic acid methylene chlorideHCID 669884123-Cyclohexylazetidin-3-ol trifluoroacetateHCID 178490239HCID 178490239, compound

Product 1

HCID 178490238HCID 178490238, compoundYield 32%

Reagents, catalysts & solvents 3

HCID 81531DiisopropylethylamineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

1 ml of a 3/2 dichloromethane/trifluoroacetic acid solution is added to 84 mg (0.193 mmol) of (S)-2-[(S)-2-benzoylamino-3-(1H-imidazol-4-yl)propionylamino]-3-(4-methoxyphenyl)propanoic acid (cf. procedure 1-1). After stirring at ambient temperature for 1 hour, the solvents are evaporated off. The residue obtained is dissolved in 1 ml of DMF, and 79 mg (0.246 mmol) of TBTU and 15 drops of DIEA are added. 0.235 mmol of 3-cyclohexylazetidin-3-ol trifluoroacetate dissolved in 1 ml of a DCM solution is added dropwise and stirred at ambient temperature for 2 hours. A saturated solution of potassium hydrogen carbonate 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 85/15 dichloro-methane/methanol mixture). 35 mg of N—[(S)-1-[(S)-2-(3-cyclohexyl-3-hydroxyazetidin-1-yl)-1-(4-methoxybenzyl)-2-oxoethylcarbamoyl]-2-(1H-imidazol-4-yl)ethyl]benzamide are obtained in the form of a yellow powder with a yield of 32%.

Workup

  1. customthe solvents are evaporated off
  2. customThe residue obtained
  3. additionis added dropwise
  4. stirringstirred at ambient temperature for 2 hours
  5. extractionfollowed by extraction with dichloromethane
  6. washThe organic phase is washed with a saturated solution of potassium hydrogen carbonate
  7. customThe organic phase is dried
  8. customevaporated to dryness
  9. customThe crude product obtained
  10. customis purified by silica gel chromatography (eluent 85/15 dichloro-methane/methanol mixture)

Sources & evidence

ORD record
ord-fc6d17876ce64712b86b33b6604db05d
Source dataset
uspto-grants-2014_10
Patent number
US08871187B2

Reaction notes

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