1-Naphthalenemethanamine, alpha-methyl-, (alphaS)- → 2-[3-(4-chlorophenyl)-4-cyclopropyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]-N-[(1S)-1-(1-naphthyl)ethyl]propionamide

HRID 660930

Reaction equation

HRID 660930 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]3[CH2:15][CH2:14]3)[C:11](=[O:16])[N:10]([CH:17]([CH3:21])[C:18]([OH:20])=O)[N:9]=2)=[CH:4][CH:3]=1.[C:22]1([C@@H:32]([NH2:34])[CH3:33])[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[CH:24][CH:23]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:12]([CH:13]3[CH2:14][CH2:15]3)[C:11](=[O:16])[N:10]([CH:17]([CH3:21])[C:18]([NH:34][C@H:32]([C:22]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH:25]=[CH:24][CH:23]=3)[CH3:33])=[O:20])[N:9]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 663251-Naphthalenemethanamine, alpha-methyl-, (alphaS)-HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 58011743Rac-2-[3-(4-chlorophenyl)-4-cyclopropyl-5-oxo-4,5-dihydro-1h-1,2,4-triazol-1-yl]propionic acid

Product 1

HCID 580116372-[3-(4-chlorophenyl)-4-cyclopropyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]-N-[(1S)-1-(1-naphthyl)ethyl]propionamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

100.0 mg (0.325 mmol) of 2-[3-(4-chlorophenyl)-4-cyclopropyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]-propionic acid from Example 105A are placed in 2 ml of DMF and treated with 61.2 mg (0.357 mmol) of (1S)-1-(1-naphthyl)ethanamine, 52.7 mg (0.390 mmol) of HOBt and 81.0 mg (0.422 mmol) of EDC hydrochloride. The mixture is stirred overnight at room temperature, then partitioned between dichloromethane and water, and the organic phase is separated, dried over sodium sulphate and concentrated. The residue is purified by flash chromato-graphy on silica gel (eluent: first dichloromethane, then dichloromethane/methanol 100:1) and then further separated by preparative HPLC on chiral phase [Method 15]. 52 mg (35% of theory) of the diastereomerically pure target compound are thus obtained (see also Example 187).

Workup

  1. custompartitioned between dichloromethane and water
  2. customthe organic phase is separated
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated
  5. customThe residue is purified by flash chromato-graphy on silica gel (eluent
  6. customfirst dichloromethane, then dichloromethane/methanol 100:1) and then further separated by preparative HPLC on chiral phase [Method 15]
  7. custom52 mg (35% of theory) of the diastereomerically pure target compound are thus obtained (

Sources & evidence

ORD record
ord-91e6e36ead9849e19f77cf636786ec83
Source dataset
uspto-grants-2011_12
Patent number
US08084481B2

Linked notes

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