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 660931

반응식

HRID 660931 반응식
[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

참가 물질

6

반응물 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

생성물 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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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 is phase 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]. 51 mg (34% of theory) of the diastereomerically pure target compound are thus obtained (see also Example 186).

후처리

  1. custompartitioned between dichloromethane and water
  2. customseparated
  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. custom51 mg (34% of theory) of the diastereomerically pure target compound are thus obtained (

출처 및 근거

ORD 기록
ord-bb65c78082ca457cad81922529a33249
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08084481B2

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