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 1455598ノート

反応式

HRID 1455598 の反応式
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]

参加物

6

反応物 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

生成物 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]-amide収率 85.6%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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

後処理

  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

出典と根拠

ORDレコード
ord-e89b73ad05ab4ac5b9ff363e21eb7125
出典データセット
uspto-grants-2009_01
特許番号
US07482448B2

反応ノート

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