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 1455596ノート

反応式

HRID 1455596 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.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

参加物

6

反応物 4

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

生成物 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)-amide収率 61.2%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-c37ddc0678d342238d981b71640c1b0a
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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