Diisopropylethylamine → (+/-)-3-({5-[1-(2,6-Dimethyl-4'-trifluoromethyl-biphenyl-4-yloxy)-ethyl]-thiophene-2-carbonyl}-amino)-propionic acid methyl ester

HRID 660983노트

반응식

HRID 660983 반응식
[CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH:9]([C:11]2[S:15][C:14]([C:16](O)=[O:17])=[CH:13][CH:12]=2)[CH3:10])[CH:5]=[C:4]([CH3:19])[C:3]=1[C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=1.Cl.[CH3:31][O:32][C:33](=[O:37])[CH2:34][CH2:35][NH2:36].O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.Cl.CN(C)CCCN=C=NCC>CN(C=O)C.O>[CH3:31][O:32][C:33](=[O:37])[CH2:34][CH2:35][NH:36][C:16]([C:14]1[S:15][C:11]([CH:9]([O:8][C:6]2[CH:7]=[C:2]([CH3:1])[C:3]([C:20]3[CH:25]=[CH:24][C:23]([C:26]([F:27])([F:28])[F:29])=[CH:22][CH:21]=3)=[C:4]([CH3:19])[CH:5]=2)[CH3:10])=[CH:12][CH:13]=1)=[O:17]

참가 물질

8

반응물 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2734767Methyl 3-aminopropanoate hydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 67485022(+/-)-5-[1-(2,6-Dimethyl-4'-trifluoromethyl-biphenyl-4-yloxy)-ethyl]-thiophene-2-carboxylic acid

생성물 1

HCID 59356032(+/-)-3-({5-[1-(2,6-Dimethyl-4'-trifluoromethyl-biphenyl-4-yloxy)-ethyl]-thiophene-2-carbonyl}-amino)-propionic acid methyl ester수율 75%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

To a mixture of (-±)-5-[1-(2,6-dimethyl-4′-trifluoromethyl-biphenyl-4-yloxy)-ethyl]-thiophene-2-carboxylic acid (0.545 g, 1.30 mmol), 3-amino-propionic acid methyl ester hydrochloride (0.199 g, 1.43 mmol), and 1-hydroxybenzotriazole hydrate (HOBt, 0.217 g, 1.60 mmol) in DMF (13.0 mL) is added N,N-diisopropylethylamine (0.67 mL, 3.84 mmol), then N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDCI, 0.330 g, 1.72 mmol) and stirred overnight. The reaction mixture is poured into H2O (25 mL) and extracted with EtOAc (3×25 mL). Combined organic extracts are washed with H2O, brine, dried over MgSO4, filtered, and concentrated. The residue is loaded onto silica gel and eluted using hexanes with an ethyl acetate gradient from 0% to 75% to provide (±)-3-({5-[1-(2,6-dimethyl-4′-trifluoromethyl-biphenyl-4-yloxy)-ethyl]-thiophene-2-carbonyl}-amino)-propionic acid methyl ester (0.490 g, 75%) as a white foam. MS (ES): 504.3 [M−H]−.

후처리

  1. extractionextracted with EtOAc (3×25 mL)
  2. washCombined organic extracts are washed with H2O, brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. washeluted

출처 및 근거

ORD 기록
ord-f1e48613793d4d68a32a3799c0173354
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08084489B2

반응 노트

불러오는 중…