Diisopropylethylamine → morpholine-4-carboxylic acid [(S)-3,3-difluoro-1-((S)-1-{hydroxy-[5-(4-trifluoromethoxy-phenyl)-1,3,4-oxadiazol-2-yl]-methyl)-propylcarbamoyl)-hexyl]-amide

HRID 1455598노트

반응식

HRID 1455598 반응식
C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[NH2:43][CH:44]([CH2:63][CH3:64])[C@@H:45]([C:47]1[O:48][C:49]([C:52]2[CH:57]=[CH:56][C:55]([O:58][C:59]([F:62])([F:61])[F:60])=[CH:54][CH:53]=2)=[N:50][N:51]=1)[OH:46].[F:65][C:66]([F:84])([CH2:81][CH2:82][CH3:83])[CH2:67][C@H:68]([NH:72][C:73]([N:75]1[CH2:80][CH2:79][O:78][CH2:77][CH2:76]1)=[O:74])[C:69](O)=[O:70]>C(Cl)Cl>[F:84][C:66]([F:65])([CH2:81][CH2:82][CH3:83])[CH2:67][C@H:68]([NH:72][C:73]([N:75]1[CH2:76][CH2:77][O:78][CH2:79][CH2:80]1)=[O:74])[C:69](=[O:70])[NH:43][C@H:44]([CH:45]([OH:46])[C:47]1[O:48][C:49]([C:52]2[CH:53]=[CH:54][C:55]([O:58][C:59]([F:61])([F:60])[F:62])=[CH:56][CH:57]=2)=[N:50][N:51]=1)[CH2:63][CH3:64]

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 57535361(S)-4,4-difluoro-2-[(morpholine-4-carbonyl)-amino]-heptanoic acidHCID 68823850(S)-2-Amino-1-[5-(4-trifluoromethoxy-phenyl)-1,3,4-oxadiazol-2-yl]-butan-1-ol

생성물 1

HCID 86607348morpholine-4-carboxylic acid [(S)-3,3-difluoro-1-((S)-1-{hydroxy-[5-(4-trifluoromethoxy-phenyl)-1,3,4-oxadiazol-2-yl]-methyl)-propylcarbamoyl)-hexyl]-amide수율 85.6%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

PyBOP (68.69 mg, 0.13 mmol), diisopropylethylamine (0.023 mL, 0.13 mmol) and (S)-2-Amino-1-[5-(4-trifluoromethoxy-phenyl)-1,3,4-oxadiazol-2-yl]-butan-1-ol (38.0 mg, 0.12 mmol) are added to a solution of (S)-4,4-Difluoro-2-[(morpholine-4-carbonyl)-amino]-heptanoic acid (34 mg, 0.12 mmol) in dry methylene chloride (4 mL) and the reaction mixture is stirred overnight at room temperature. The reaction is quenched with aqueous NaHCO3, extracted twice with methylene chloride, the organic extracts are dried over Na2SO4 and evaporated under reduced pressure. Column chromatography on silica eluting with a mixture of methylene chloride and ethyl acetate gives morpholine-4-carboxylic acid [(S)-3,3-difluoro-1-((S)-1-{hydroxy-[5-(4-trifluoromethoxy-phenyl)-1,3,4-oxadiazol-2-yl]-methyl}-propylcarbamoyl)-hexyl]-amide as a solid (61 mg). LC/MS 71%, M+1=594

후처리

  1. customThe reaction is quenched with aqueous NaHCO3
  2. extractionextracted twice with methylene chloride
  3. dry with materialthe organic extracts are dried over Na2SO4
  4. customevaporated under reduced pressure
  5. additionColumn chromatography on silica eluting with a mixture of methylene chloride and ethyl acetate

출처 및 근거

ORD 기록
ord-e89b73ad05ab4ac5b9ff363e21eb7125
출처 데이터셋
uspto-grants-2009_01
특허 번호
US07482448B2

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