1,2-Dichloroethane → tert-butyl (2S)-2-{2-(4-fluorophenethyl)-5-[1-(thiazol-2-yl)-2-(1-methylimidazol-5-yl)ethoxy]benzoylamino}-4-methylsulfanylbutyrate

HRID 1251932Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1251932
[F:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][CH2:7][C:8]2[CH:16]=[CH:15][C:14]([O:17][CH:18]([C:26]3[S:27][CH:28]=[CH:29][N:30]=3)[CH2:19][C:20]3[N:24]([CH3:25])[CH:23]=[N:22][CH:21]=3)=[CH:13][C:9]=2[C:10](O)=[O:11])=[CH:4][CH:3]=1.Cl.[C:34]([O:38][C:39](=[O:46])[C@H:40]([CH2:42][CH2:43][S:44][CH3:45])[NH2:41])([CH3:37])([CH3:36])[CH3:35].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CN(C1C=CN=CC=1)C.CN(C=O)C>[F:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][CH2:7][C:8]2[CH:16]=[CH:15][C:14]([O:17][CH:18]([C:26]3[S:27][CH:28]=[CH:29][N:30]=3)[CH2:19][C:20]3[N:24]([CH3:25])[CH:23]=[N:22][CH:21]=3)=[CH:13][C:9]=2[C:10]([NH:41][C@@H:40]([CH2:42][CH2:43][S:44][CH3:45])[C:39]([O:38][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:46])=[O:11])=[CH:4][CH:3]=1

Komponenten

7

Edukt 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 13141795h-Met-otbu.hclHCID 183244782-(4-Fluorophenethyl)-5-[2-(1-methylimidazol-5-yl)1-(thiazol-2-yl)ethoxy]benzoic acid

Produkt 1

HCID 57100633tert-butyl (2S)-2-{2-(4-fluorophenethyl)-5-[1-(thiazol-2-yl)-2-(1-methylimidazol-5-yl)ethoxy]benzoylamino}-4-methylsulfanylbutyrate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A mixture of 2-(4-fluorophenethyl)-5-[2-(1-methylimidazol-5-yl)-1-(thiazol-2-yl)ethoxy]benzoic acid (0.74 g, 1.63 mmol), DMAP (1.0 g, 8.2 mmol), L-methionine tert-butyl ester HCl (1.0 g, 4.92 mmol), EDC (0.63 g, 3.27 mmol) and HOBT (0.22 g, 1.63 mmol) in DMF (50 ml) was stirred at ambient temperature under a nitrogen atmosphere for 16 hours. The reaction was evaporated to dryness and washed with aqueous citric acid (1M, 20 ml) and extracted with dichloromethane (20 ml). The extracts were washed with saturated brine and dried and applied directly onto a silica flash column which was eluted with ethyl acetate/methanol (9:1 and 4:1) to give tert-butyl (2S)-2- {2-(4-fluorophenethyl)-5-[1-(thiazol-2-yl)-2-(1-methylimidazol-5-yl)ethoxy]benzoylamino}-4-methylsulfanylbutyrate. The product was dissolved in ethyl acetate and treated with 1M ethereal HCl (10 ml). The resulting solid was isolated by centrifuging, flirther washing with diethyl ether and finally drying under high vacuum to give tert-butyl (2S)-2-{2-(4-fluorophenethyl)-5-[1-(thiazol-2-yl)-2-(1-methylimidazol-5-yl)ethoxy]benzoylamino}-4-methylsulfanylbutyrate as a white solid, (0.57 g, 54% Yield).

Aufarbeitung

  1. customThe reaction was evaporated to dryness
  2. washwashed with aqueous citric acid (1M, 20 ml)
  3. extractionextracted with dichloromethane (20 ml)
  4. washThe extracts were washed with saturated brine
  5. customdried
  6. washwas eluted with ethyl acetate/methanol (9:1 and 4:1)

Quellen und Nachweise

ORD-Eintrag
ord-17a109ca2faf4735830bad7657aaf5aa
Quelldatensatz
uspto-grants-2002_01
Patentnummer
US06342765B1

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