Lithium Hydroxide → N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[4-(2-hydroxyethyl)-1,3-oxazol-2-yl]benzamide

HRID 348872

反応式

HRID 348872 の反応式
C([O:8][CH2:9][CH2:10][C:11]1[N:12]=[C:13]([C:16]2[CH:17]=[C:18]([CH:23]=[CH:24][CH:25]=2)[C:19]([O:21]C)=O)[O:14][CH:15]=1)C1C=CC=CC=1.C1CCCCC=1.[OH-].[Li+].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.Cl.[NH2:69][C@@H:70]([CH2:84][C:85]1[CH:90]=[C:89]([F:91])[CH:88]=[C:87]([F:92])[CH:86]=1)[C@H:71]([OH:83])[CH2:72][NH:73][CH2:74][C:75]1[CH:80]=[CH:79][CH:78]=[C:77]([CH2:81][CH3:82])[CH:76]=1>C(O)C.C(Cl)(Cl)Cl.[OH-].[Pd+2].[OH-]>[F:91][C:89]1[CH:90]=[C:85]([CH:86]=[C:87]([F:92])[CH:88]=1)[CH2:84][C@H:70]([NH:69][C:19](=[O:21])[C:18]1[CH:23]=[CH:24][CH:25]=[C:16]([C:13]2[O:14][CH:15]=[C:11]([CH2:10][CH2:9][OH:8])[N:12]=2)[CH:17]=1)[C@H:71]([OH:83])[CH2:72][NH:73][CH2:74][C:75]1[CH:80]=[CH:79][CH:78]=[C:77]([CH2:81][CH3:82])[CH:76]=1

参加物

10

反応物 6

HCID 3939Lithium HydroxideHCID 8079CyclohexeneHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21086153Methyl 3-{4-[2-(benzyloxy)ethyl]-1,3-oxazol-2-yl}benzoateHCID 57487281(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride

生成物 1

HCID 58802533N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[4-(2-hydroxyethyl)-1,3-oxazol-2-yl]benzamide

試薬・触媒・溶媒 3

HCID 9942167Palladium hydroxide触媒HCID 702Ethanol溶媒HCID 6212Chloroform溶媒

実験手順

Methyl 3-{4-[2-(benzyloxy)ethyl]-1,3-oxazol-2-yl}benzoate (300 mg, 0.9 mmol), 20% palladium(II) hydroxide on carbon (65 mg), and cyclohexene (3 mL) in absolute ethanol (3 mL) are refluxed 1 h. The reaction is cooled, filtered through diatomaceous earth, and concentrated under reduced pressure. The residue is redissolved in 2:1:1 tetrahydrofuran/methanol/water (4 mL) is added lithium hydroxide (75 mg, 1.8 mmol). The reaction mixture is stirred at room temperature for 3 h, and concentrated under reduced pressure. The residue is dissolved in DMF (5 mL), and diisopropylethylamine (625 μL, 3.6 mmol), HATU (540 mg, 1.4 mmol), and (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride prepared by the method in EXAMPLE SP-272 (407 mg, 1 mmol) are added. The reaction stirred at room temperature 16 h. The reaction mixture is diluted with chloroform, washed with water, 1N hydrochloric acid (aq), saturated sodium bicarbonate, brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 8% methanol/chloroform) provides the title compound. ESI MS m/z 550.3 [M+H]+.

後処理

  1. temperatureThe reaction is cooled
  2. filtrationfiltered through diatomaceous earth
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue is redissolved in 2:1:1 tetrahydrofuran/methanol/water (4 mL)
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe residue is dissolved in DMF (5 mL)
  7. additionare added
  8. stirringThe reaction stirred at room temperature 16 h
  9. washwashed with water, 1N hydrochloric acid (aq), saturated sodium bicarbonate, brine
  10. dry with materialdried (sodium sulfate)
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customPurification by flash column chromatography (silica, 8% methanol/chloroform)

出典と根拠

ORDレコード
ord-bf61433bd58e403bb20367b857a0c47a
出典データセット
uspto-grants-2007_02
特許番号
US07176242B2

関連ノート

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