Diisopropylethylamine → Ethyl (s)-3-((s)-2-(4,4-bis(trifluoromethyl)-3-(4-(3-(2-methylphenyl)ureido)-3-methoxybenzyl)-2,5-dioxoimidazolidin-1-yl)-2-(2-methylpropyl)acetylamino)-3-phenylpropionate

HRID 1840625

반응식

HRID 1840625 반응식
[B-](F)(F)(F)F.CCOC(C(C#N)=NOC(N(C)C)=[N+](C)C)=O.C(N(CC)C(C)C)(C)C.[F:32][C:33]([F:74])([F:73])[C:34]1([C:69]([F:72])([F:71])[F:70])[C:38](=[O:39])[N:37]([C@@H:40]([CH2:44][CH:45]([CH3:47])[CH3:46])[C:41](O)=[O:42])[C:36](=[O:48])[N:35]1[CH2:49][C:50]1[CH:55]=[CH:54][C:53]([NH:56][C:57]([NH:59][C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=2[CH3:66])=[O:58])=[C:52]([O:67][CH3:68])[CH:51]=1.[NH2:75][C@H:76]([C:83]1[CH:88]=[CH:87][CH:86]=[CH:85][CH:84]=1)[CH2:77][C:78]([O:80][CH2:81][CH3:82])=[O:79]>CN(C=O)C>[F:72][C:69]([F:70])([F:71])[C:34]1([C:33]([F:74])([F:73])[F:32])[C:38](=[O:39])[N:37]([C@@H:40]([CH2:44][CH:45]([CH3:46])[CH3:47])[C:41]([NH:75][C@H:76]([C:83]2[CH:88]=[CH:87][CH:86]=[CH:85][CH:84]=2)[CH2:77][C:78]([O:80][CH2:81][CH3:82])=[O:79])=[O:42])[C:36](=[O:48])[N:35]1[CH2:49][C:50]1[CH:55]=[CH:54][C:53]([NH:56][C:57]([NH:59][C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=2[CH3:66])=[O:58])=[C:52]([O:67][CH3:68])[CH:51]=1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 915085(S)-Ethyl 3-amino-3-phenylpropanoateHCID 2733286O-[(Ethoxycarbonyl)cyanomethylenamino]-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 87951373(s)-2-(4,4-Bis(trifluoromethyl)-3-(4-(3-(2-methylphenyl)ureido)-3-methoxybenzyl)-2,5-dioxoimidazolidin-1-yl)-2-(2-methylpropyl)acetic acid

생성물 1

HCID 91066696Ethyl (s)-3-((s)-2-(4,4-bis(trifluoromethyl)-3-(4-(3-(2-methylphenyl)ureido)-3-methoxybenzyl)-2,5-dioxoimidazolidin-1-yl)-2-(2-methylpropyl)acetylamino)-3-phenylpropionate수율 71.2%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

1.89 g (5.77 mmol) of TOTU and 932 μL of N,N-diisopropylethylamine were added at 0° C. to a solution of 3.57 g (5.77 mmol) of (S)-2-(4,4-bis(trifluoromethyl)-3-(4-(3-(2-methylphenyl)ureido)-3-methoxybenzyl)-2, 5-dioxoimidazolidin-1-yl)-2-(2-methylpropyl)acetic acid (prepared from (S)-2-(4,4-bis(trifluoromethyl)-2,5-dioxoimidazolidin-1-yl)-2-(2-methylpropyl)acetic acid and 4-(3-(2-methylphenyl)ureido)-3-methoxybenzyl chloride as described in Example 18f) and 1.11 g (5.77 mmol) of ethyl (S)-3-amino-3-phenylpropionate in 30 mL of absolute DMF. After stirring at room temperature for 1 hour, DMF was removed in vacuo, the residue was taken up in ethyl acetate and the ethyl acetate solution was washed successively with an aqueous KHSO4K2SO4 solution, a saturated NaHCO3 solution and water. After drying the organic phase over sodium sulfate and filtering, the solvent was removed in vacuo and the residue was chromatographed over silica gel using ethyl acetate/heptane (2/3). After concentration of the product fractions, 3.26 g (71%) of the title compound were obtained.

후처리

  1. customDMF was removed in vacuo
  2. washthe ethyl acetate solution was washed successively with an aqueous KHSO4K2SO4 solution
  3. dry with materialAfter drying the organic phase over sodium sulfate
  4. filtrationfiltering
  5. customthe solvent was removed in vacuo
  6. customthe residue was chromatographed over silica gel

출처 및 근거

ORD 기록
ord-9df09ac466a34b57b17d0a07ae4c3dd5
출처 데이터셋
uspto-grants-2004_01
특허 번호
US06680333B2

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