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Diisopropylethylamine → 3-(4-Benzyloxy-phenyl)-2-[4-methyl-2-(morpholine-4-sulfonylamino)-pentanoylamino]-propionic acid tert-butyl ester

HRID 2230322
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HRID 2230322 반응식
[C:1]([O:5][C:6](=[O:32])[CH:7]([NH:23][C:24](=[O:31])[CH:25]([NH2:30])[CH2:26][CH:27]([CH3:29])[CH3:28])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:11][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[N:33]1([S:39](Cl)(=[O:41])=[O:40])[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1.C(N(CC)C(C)C)(C)C>CN(C1C=CN=CC=1)C.C1C=CC=CC=1>[C:1]([O:5][C:6](=[O:32])[CH:7]([NH:23][C:24](=[O:31])[CH:25]([NH:30][S:39]([N:33]1[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1)(=[O:41])=[O:40])[CH2:26][CH:27]([CH3:28])[CH3:29])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:11][CH:10]=1)([CH3:3])([CH3:2])[CH3:4]
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참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 12798265Morpholine-4-sulfonyl chlorideHCID 540817292-(2-Amino-4-methyl-pentanoylamino)-3-(4-benzyloxy-phenyl)-propionic acid tert-butyl ester

생성물 1

HCID 700611183-(4-Benzyloxy-phenyl)-2-[4-methyl-2-(morpholine-4-sulfonylamino)-pentanoylamino]-propionic acid tert-butyl ester수율 65%

시약·촉매·용매 2

HCID 14284
4-(Dimethylamino)pyridine
촉매
HCID 241Benzene용매

실험 절차

A solution of the product from Example AI ([S-(R*,R*)]-2-(2-amino-4-methyl-pentanoylamino)-3-(4-benzyloxy-phenyl)-propionic acid tert-butyl ester) (397 mg, 0.90 mmol), morpholine-4-sulphonyl chloride (334 mg, 1.8 mmol, prepared by the method of von Geldem, et al., J. Med. Chem., 1996;39:968-981), N,N-diisopropylethyl-amine (246 mg, 1.9 mmol), and DMAP (25 mg) in benzene (5 mL) was heated under reflux for 3 hours, then concentrated in vacuo and the residue dissolved in ethyl acetate, and washed with saturated NaHCO3 solution, water and brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The amber oil thus obtained was purified via flash chromatography (silica gel, 35% EtOAc/Hexane) to give 346 mg (65%) of the title compound as a yellow foam, mp=54-57° C.

후처리

  1. temperatureunder reflux for 3 hours
  2. concentrationconcentrated in vacuo
  3. dissolutionthe residue dissolved in ethyl acetate
  4. washwashed with saturated NaHCO3 solution, water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe amber oil thus obtained
  8. customwas purified via flash chromatography (silica gel, 35% EtOAc/Hexane)

출처 및 근거

ORD 기록
ord-39e6773876a340948784f1b127d6be19
출처 데이터셋
uspto-grants-2002_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06423689B1

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