4-Methylmorpholine → 1,1-dimethylethyl (3R)-3-(cyclopentylmethyl)-4-(5-{[(6-ethyl-2-pyridinyl)amino]carbonyl}-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoate

HRID 1396970ノート

反応式

HRID 1396970 の反応式
[CH:1]1([CH2:6][C@H:7]([CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C:8]([N:10]2[CH:14]([C:15](O)=[O:16])[CH2:13][CH:12]=[N:11]2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.CN1CCOCC1.[CH2:50]([C:52]1[N:57]=[C:56]([NH2:58])[CH:55]=[CH:54][CH:53]=1)[CH3:51]>C(#N)C>[CH:1]1([CH2:6][C@@H:7]([C:8]([N:10]2[CH:14]([C:15]([NH:58][C:56]3[CH:55]=[CH:54][CH:53]=[C:52]([CH2:50][CH3:51])[N:57]=3)=[O:16])[CH2:13][CH:12]=[N:11]2)=[O:9])[CH2:18][C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])[CH2:2][CH2:3][CH2:4][CH2:5]1

参加物

6

反応物 4

HCID 79724-MethylmorpholineHCID 890216-Ethylpyridin-2-amineHCID 27340604-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-iumHCID 682877191-{(2R)-2-(cyclopentylmethyl)-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoyl}-4,5-dihydro-1H-pyrazole-5-carboxylic acid

生成物 1

HCID 682879751,1-dimethylethyl (3R)-3-(cyclopentylmethyl)-4-(5-{[(6-ethyl-2-pyridinyl)amino]carbonyl}-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoate収率 79%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

To a solution of 1-{(2R)-2-(cyclopentylmethyl)-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoyl}-4,5-dihydro-1H-pyrazole-5-carboxylic acid (352 mg, 1.0 mmol) in acetonitrile (10 mL) at 0° C. was added 4-[4,6-bis(methyloxy)-1,3,5-triazin-2-yl]-4-methylmorpholin-4-ium (656 mg, 2.0 mmol) and N-methylmorpholine (0.28 mL, 2.5 mmol). The reaction mixture was stirred for 2 hours. After this time, 6-ethyl-2-pyridinamine (159 mg, 1.3 mmol) was added to the mixture, which was then allowed to warm to room temperature and stirred for 3 hours. The solvent was removed under reduced pressure, and water (5 mL) and DCM (15 mL) were added to the resulting residue. The phases were separated. The aqueous phase was extracted twice with DCM (15 mL), and the combined organic phases were dried over sodium sulfate and concentrated. The crude product residue was purified by Combiflash silica gel chromatography (0-100% EtOAc in hex) to provide 1,1-dimethylethyl (3R)-3-(cyclopentylmethyl)-4-(5-{[(6-ethyl-2-pyridinyl)amino]carbonyl}-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoate (359 mg, 0.79 mmol, 79% yield) as a clear oil. MS: 457 ([M+H]+).

後処理

  1. stirringstirred for 3 hours
  2. customThe solvent was removed under reduced pressure, and water (5 mL) and DCM (15 mL)
  3. additionwere added to the resulting residue
  4. customThe phases were separated
  5. extractionThe aqueous phase was extracted twice with DCM (15 mL)
  6. dry with materialthe combined organic phases were dried over sodium sulfate
  7. concentrationconcentrated
  8. customThe crude product residue was purified by Combiflash silica gel chromatography (0-100% EtOAc in hex)

出典と根拠

ORDレコード
ord-c8e86cde5be74d63a582e12f5f973b26
出典データセット
uspto-grants-2014_12
特許番号
US08901119B2

反応ノート

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