1,2-Dichloroethane → {2-[1-(4-Cyano-3-fluoro-phenyl)-1-(3-methyl-3H-imidazol-4-yl)-ethylcarbamoyl]-ethyl}-carbamic acid

HRID 1060884Notes

Reaction equation

HRID 1060884 reaction equation
C([O:5][C:6]([NH:8][CH2:9][CH2:10][C:11]([OH:13])=O)=[O:7])(C)(C)C.N1C2C(=NC=CC=2)N(O)N=1.C(Cl)CCl.CN1CCOCC1.[NH2:35][C:36]([C:44]1[CH:51]=[CH:50][C:47]([C:48]#[N:49])=[C:46]([F:52])[CH:45]=1)([C:38]1[N:39]([CH3:43])[CH:40]=[N:41][CH:42]=1)[CH3:37]>CN(C=O)C>[C:48]([C:47]1[CH:50]=[CH:51][C:44]([C:36]([NH:35][C:11]([CH2:10][CH2:9][NH:8][C:6](=[O:7])[OH:5])=[O:13])([C:38]2[N:39]([CH3:43])[CH:40]=[N:41][CH:42]=2)[CH3:37])=[CH:45][C:46]=1[F:52])#[N:49]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 76809N-((1,1-dimethylethoxy)carbonyl)-beta-alanineHCID 181649HOAtHCID 11470581(+)-4-[1-amino-1-(3-methyl-3H-imidazol-4-yl)-ethyl]-2-fluoro-benzonitrile

Product 1

HCID 70025288{2-[1-(4-Cyano-3-fluoro-phenyl)-1-(3-methyl-3H-imidazol-4-yl)-ethylcarbamoyl]-ethyl}-carbamic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-tert-butoxycarbonylamino-propionic acid (0.77 g, 4.09 mmol) in DMF (8.2 mL) at ambient temperature was added [1,2,3]triazolo[4,5-b]pyridin-3-ol (HOAT) (0.53 g, 3.89 mmol), EDC (0.82 g, 4.30 mmol), and 4-methylmorpholine (0.41 g, 4.09 mmol), followed by (+)-4-[1-amino-1-(3-methyl-3H-imidazol-4-yl)-ethyl]-2-fluoro-benzonitrile (Example 1, Step I) (1.00 g, 4.09 mmol). After stirring overnight, the reaction was concentrated in vacuo to remove the DMF. The residue was partitioned between EtOAc and saturated aqueous NaHCO3 solution, the organic layer washed with brine, dried (Na2SO4), and concentrated in vacuo to provide the crude title compound.

Workup

  1. concentrationthe reaction was concentrated in vacuo
  2. customto remove the DMF
  3. customThe residue was partitioned between EtOAc and saturated aqueous NaHCO3 solution
  4. washthe organic layer washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-97dadc4a13ae421fa9725a7fbfe48654
Source dataset
uspto-grants-2003_02
Patent number
US06525074B2

Reaction notes

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