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

HRID 1455596노트

반응식

HRID 1455596 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.FC(F)(F)C(O)=O.[NH2:50][CH:51]([CH2:62][CH3:63])[C@@H:52]([C:54]1[O:55][C:56]([CH:59]2[CH2:61][CH2:60]2)=[N:57][N:58]=1)[OH:53].[F:64][C:65]([F:83])([CH2:80][CH2:81][CH3:82])[CH2:66][C@H:67]([NH:71][C:72]([N:74]1[CH2:79][CH2:78][O:77][CH2:76][CH2:75]1)=[O:73])[C:68](O)=[O:69]>C(Cl)Cl>[CH:59]1([C:56]2[O:55][C:54]([CH:52]([OH:53])[C@@H:51]([NH:50][C:68]([C@@H:67]([NH:71][C:72]([N:74]3[CH2:79][CH2:78][O:77][CH2:76][CH2:75]3)=[O:73])[CH2:66][C:65]([F:83])([F:64])[CH2:80][CH2:81][CH3:82])=[O:69])[CH2:62][CH3:63])=[N:58][N:57]=2)[CH2:61][CH2:60]1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 57535361(S)-4,4-difluoro-2-[(morpholine-4-carbonyl)-amino]-heptanoic acidHCID 68822405HCID 68822405, 화합물

생성물 1

HCID 86607347morpholine-4-carboxylic acid ((S)-1-{(S)-1-[(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-hydroxy-methyl]-propylcarbamoyl-}3,3-difluoro-hexyl)-amide수율 61.2%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

PyBOP (171.73 mg, 0.33 mmol), diisopropylethylamine (0.0575 mL, 0.33 mmol) and (S)-2-amino-1-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-butan-1-ol; compound with trifluoro-acetic acid (0.30 mmol) are added to a solution of (S)-4,4-Difluoro-2-[(morpholine-4-carbonyl)-amino]-heptanoic acid (88.29 mg, 0.30 mmol) in dry methylene chloride (4 mL) and the reaction mixture is stirred overnight at room temperature. The reaction is quenched with aqueous sodium bicarbonate, extracted twice with methylene chloride, the organic extracts are dried over sodium sulfate 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)-1-{(S)-1-[(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-hydroxy-methyl]-propylcarbamoyl-}3,3-difluoro-hexyl)-amide as a solid (87 mg). LC/MS 97%, 474 (M+1).

후처리

  1. customThe reaction is quenched with aqueous sodium bicarbonate
  2. extractionextracted twice with methylene chloride
  3. dry with materialthe organic extracts are dried over sodium sulfate
  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-c37ddc0678d342238d981b71640c1b0a
출처 데이터셋
uspto-grants-2009_01
특허 번호
US07482448B2

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