Triethylamine → N-[(R)-2-(3-but-2-ynyloxy-3-o-tolylazetidin-1-yl)-1-(4-methoxybenzyl)-2-oxoethyl]-3-(5-methyl-1H-imidazol-4-yl)propionamide

HRID 540436Notes

Reaction equation

HRID 540436 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)CC)C.Cl.[CH3:31][C:32]1[NH:36][CH:35]=[N:34][C:33]=1[CH2:37][CH2:38][C:39]([OH:41])=O.[NH2:42][C@H:43]([CH2:62][C:63]1[CH:68]=[CH:67][C:66]([O:69][CH3:70])=[CH:65][CH:64]=1)[C:44]([N:46]1[CH2:49][C:48]([O:57][CH2:58][C:59]#[C:60][CH3:61])([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][C:51]=2[CH3:56])[CH2:47]1)=[O:45].[OH-].[Na+]>CN(C)C=O>[CH2:58]([O:57][C:48]1([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][C:51]=2[CH3:56])[CH2:49][N:46]([C:44](=[O:45])[C@H:43]([NH:42][C:39](=[O:41])[CH2:38][CH2:37][C:33]2[N:34]=[CH:35][NH:36][C:32]=2[CH3:31])[CH2:62][C:63]2[CH:68]=[CH:67][C:66]([O:69][CH3:70])=[CH:65][CH:64]=2)[CH2:47]1)[C:59]#[C:60][CH3:61]

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 66988366(R)-2-amino-1-(3-but-2-ynyloxy-3-o-tolyl-azetidin-1-yl)-3-(4-methoxyphenyl)propan-1-one

Product 1

HCID 46194192N-[(R)-2-(3-but-2-ynyloxy-3-o-tolylazetidin-1-yl)-1-(4-methoxybenzyl)-2-oxoethyl]-3-(5-methyl-1H-imidazol-4-yl)propionamideYield 9.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

389 mg (1.2 mmol) of TBTU and 0.5 ml (3.7 mmol) of triethylamine are added to a solution containing 229 mg (1.2 mmol) of 3-(5-methyl-1H-imidazol-4-yl)propanoic acid hydrochloride in 4 ml of dimethylformamide. After 5 min, 402 mg (0.9 mmol) of (R)-2-amino-1-(3-but-2-ynyloxy-3-o-tolylazetidin-1-yl)-3-(4-methoxyphenyl)-propan-1-one dissolved in 4 ml of dimethylformamide are added. The reaction medium is then stirred for 90 h at ambient temperature, and then a 1N aqueous solution of sodium hydroxide is added and the medium is extracted with a 1/1 heptane/ethyl acetate mixture. The organic phase is washed with a saturated aqueous solution of sodium chloride and then dried over sodium sulphate, filtered and concentrated. The residue obtained is purified by silica gel chromatography, elution being carried out with an 88/12 dichloromethane/methanol mixture. 45 mg of N—[(R)-2-(3-but-2-ynyloxy-3-o-tolyl-azetidin-1-yl)-1-(4-methoxybenzyl)-2-oxoethyl]-3-(5-methyl-1H-imidazol-4-yl)propionamide are obtained in the form of a white solid with a yield of 9%.

Workup

  1. additionare added
  2. extractionthe medium is extracted with a 1/1 heptane/ethyl acetate mixture
  3. washThe organic phase is washed with a saturated aqueous solution of sodium chloride
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue obtained
  8. customis purified by silica gel chromatography, elution

Sources & evidence

ORD record
ord-a361a011dce14d01ab415eb36471fb92
Source dataset
uspto-grants-2014_10
Patent number
US08871187B2

Reaction notes

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