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 1251932노트

반응식

HRID 1251932 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6228Dimethylformamide용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-17a109ca2faf4735830bad7657aaf5aa
출처 데이터셋
uspto-grants-2002_01
특허 번호
US06342765B1

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