2,6-Lutidine → Tert-Butyl(2R,5R)-2,5-bis {2-[2-({(2S)-2-[(methoxycarbonyl)amino]-3,3-diphenyl propanoyl}amino)phenyl]ethyl}morpholine-4-carboxylate

HRID 629726노트

반응식

HRID 629726 반응식
[CH3:1][O:2][C:3]([NH:5][C@@H:6](C(C1C=CC=CC=1)C1C=CC=CC=1)[C:7](O)=[O:8])=[O:4].CN(C(ON1N=N[C:33]2[CH:34]=[CH:35][CH:36]=N[C:32]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.N1[C:52]([CH3:53])=[CH:51][CH:50]=[CH:49][C:48]=1[CH3:54].[NH2:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=1[CH2:62][CH2:63][C@H:64]1[N:69]([C:70]([O:72][C:73]([CH3:76])([CH3:75])[CH3:74])=[O:71])[CH2:68][C@@H:67]([CH2:77][CH2:78][C:79]2[CH:84]=[CH:83][CH:82]=[CH:81][C:80]=2[NH:85][C:86](=[O:106])[C@@H:87]([NH:101][C:102]([O:104][CH3:105])=[O:103])[CH:88]([C:95]2[CH:100]=[CH:99][CH:98]=[CH:97][CH:96]=2)[C:89]2[CH:94]=[CH:93][CH:92]=[CH:91][CH:90]=2)[O:66][CH2:65]1.[C:107](=O)(O)[O-].[Na+]>CN(C=O)C.C(OCC)(=O)C>[CH3:105][O:104][C:102]([NH:101][C@@H:87]([CH:88]([C:95]1[CH:100]=[CH:99][CH:98]=[CH:97][CH:96]=1)[C:89]1[CH:90]=[CH:91][CH:92]=[CH:93][CH:94]=1)[C:86]([NH:85][C:80]1[CH:81]=[CH:82][CH:83]=[CH:84][C:79]=1[CH2:78][CH2:77][C@H:67]1[O:66][CH2:65][C@@H:64]([CH2:63][CH2:62][C:57]2[CH:58]=[CH:59][CH:60]=[CH:61][C:56]=2[NH:55][C:7](=[O:8])[C@@H:6]([NH:5][C:3]([O:2][CH3:1])=[O:4])[CH:48]([C:54]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:49]2[CH:107]=[CH:53][CH:52]=[CH:51][CH:50]=2)[N:69]([C:70]([O:72][C:73]([CH3:74])([CH3:75])[CH3:76])=[O:71])[CH2:68]1)=[O:106])=[O:103]

참가 물질

8

반응물 5

HCID 79372,6-LutidineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10017620(S)-2-methoxycarbonylamino-3,3-diphenyl-propionic acidHCID 86726326tert-Butyl(2R,5R)-5-[2-(2-aminophenyl)ethyl]-2-{2-[2-({(2S)-2-[(methoxycarbonyl)amino]-3,3-diphenylpropanoyl}amino)phenyl]ethyl}morpholine-4-carboxylate

생성물 1

HCID 86726328Tert-Butyl(2R,5R)-2,5-bis {2-[2-({(2S)-2-[(methoxycarbonyl)amino]-3,3-diphenyl propanoyl}amino)phenyl]ethyl}morpholine-4-carboxylate

시약·촉매·용매 2

HCID 6228Dimethylformamide용매2회HCID 8857Ethyl Acetate용매

실험 절차

(2S)-2-[(methoxycarbonyl)amino]-3,3-diphenylpropanoic acid (1.2 equiv), HATU (1.4 equiv) and 2,6-lutidine (2.0 equiv) were combined in DMF (0.2 M vs aniline). tert-Butyl(2R,5R)-5-[2-(2-aminophenyl)ethyl]-2-{2-[2-({(2S)-2-[(methoxycarbonyl)amino]-3,3-diphenylpropanoyl}amino)phenyl]ethyl}morpholine-4-carboxylate (1.0 equiv) was dissolved in DMF (0.11 M) and was added to the reaction mixture. The reaction was stirred at room temperature for 18 h and ethyl acetate and saturated sodium bicarbonate were added. Aqueous layer was extracted twice with ethyl acetate and combined organic layers were washed with brine, 10% aqueous lithium chloride, 1N HCl, brine, dried (Na2SO4), filtered and concentrated. The crude product was purified using automated silica-gel flash chromatography using a solvent gradient of 5% to 60% of ethyl acetate and hexanes.

후처리

  1. additionwas added to the reaction mixture
  2. extractionAqueous layer was extracted twice with ethyl acetate
  3. washwere washed with brine, 10% aqueous lithium chloride, 1N HCl, brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified

출처 및 근거

ORD 기록
ord-606c0d31f8ca4b5ea9d7ee20c554f6ab
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09315475B2

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