Triethylamine → N-[(R)-2-(3-cyclohexyl-3-pentylazetidin-1-yl)-1-(4-methoxybenzyl)-2-oxoethyl]-3-(1H-imidazol-4-yl)propionamide

HRID 540404Notes

Reaction equation

HRID 540404 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)CC)C.Cl.[NH:31]1[CH:35]=[C:34]([CH2:36][CH2:37][C:38]([OH:40])=O)[N:33]=[CH:32]1.[NH2:41][C@H:42]([CH2:60][C:61]1[CH:66]=[CH:65][C:64]([O:67][CH3:68])=[CH:63][CH:62]=1)[C:43]([N:45]1[CH2:48][C:47]([CH:54]2[CH2:59][CH2:58][CH2:57][CH2:56][CH2:55]2)([CH2:49][CH2:50][CH2:51][CH2:52][CH3:53])[CH2:46]1)=[O:44]>CN(C=O)C>[CH:54]1([C:47]2([CH2:49][CH2:50][CH2:51][CH2:52][CH3:53])[CH2:46][N:45]([C:43](=[O:44])[C@H:42]([NH:41][C:38](=[O:40])[CH2:37][CH2:36][C:34]3[N:33]=[CH:32][NH:31][CH:35]=3)[CH2:60][C:61]3[CH:62]=[CH:63][C:64]([O:67][CH3:68])=[CH:65][CH:66]=3)[CH2:48]2)[CH2:59][CH2:58][CH2:57][CH2:56][CH2:55]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 66988216(R)-2-amino-1-(3-cyclohexyl-3-pentylazetidin-1-yl)-3-(4-methoxyphenyl)propan-1-oneHCID 178479756HCID 178479756, compound

Product 1

HCID 178442040N-[(R)-2-(3-cyclohexyl-3-pentylazetidin-1-yl)-1-(4-methoxybenzyl)-2-oxoethyl]-3-(1H-imidazol-4-yl)propionamideYield 55.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

100 mg (0.311 mmol) of TBTU and 0.1 ml (0.715 mmol) of triethylamine are added to 55 mg (0.311 mmol) of 3-(1H-imidazol-4-yl)propionic acid hydrochloride in 1 ml of DMF. After 10 minutes, 99 mg (0.256 mmol) of (R)-2-amino-1-(3-cyclohexyl-3-pentylazetidin-1-yl)-3-(4-methoxyphenyl)propan-1-one dissolved in 1 ml of DMF are added. After stirring for 118 hours at ambient temperature, the reaction medium is extracted with a 1/2 heptane/EtOAc mixture and washed with 1N sodium hydroxide and a saturated sodium chloride solution. The organic phase is dried over MgSO4, filtered and concentrated. The residue is purified on a silica column (eluent 9/1 DCM/MeOH). 72 mg of N—[(R)-2-(3-cyclohexyl-3-pentylazetidin-1-yl)-1-(4-methoxybenzyl)-2-oxoethyl]-3-(1H-imidazol-4-yl)propionamide are obtained in the form of a white powder, with a yield of 55%.

Workup

  1. additionare added
  2. extractionthe reaction medium is extracted with a 1/2 heptane/EtOAc mixture
  3. washwashed with 1N sodium hydroxide
  4. dry with materialThe organic phase is dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue is purified on a silica column (eluent 9/1 DCM/MeOH)

Sources & evidence

ORD record
ord-b7eb84185f174481abc4a67d945c4084
Source dataset
uspto-grants-2014_10
Patent number
US08871187B2

Reaction notes

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