Dichloromethane → N-{(1S,2R)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[(2-methoxyethyl)(methyl)amino]methyl}-5-methylbenzamide Dihydrochloride

HRID 348919

Reaktionsgleichung

Reaktionsgleichung von HRID 348919
[CH3:1][O:2][CH2:3][CH2:4][N:5]([CH2:7][C:8]1[CH:9]=[C:10]([CH:14]=[C:15]([CH3:17])[CH:16]=1)[C:11]([OH:13])=O)[CH3:6].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.C(N(CC)C(C)C)(C)C.[NH2:61][C@@H:62]([CH2:76][C:77]1[CH:82]=[C:81]([F:83])[CH:80]=[C:79]([F:84])[CH:78]=1)[C@H:63]([OH:75])[CH2:64][NH:65][CH2:66][C:67]1[CH:72]=[CH:71][CH:70]=[C:69]([CH2:73][CH3:74])[CH:68]=1.C(Cl)[Cl:86]>>[ClH:86].[ClH:86].[F:83][C:81]1[CH:82]=[C:77]([CH:78]=[C:79]([F:84])[CH:80]=1)[CH2:76][C@H:62]([NH:61][C:11](=[O:13])[C:10]1[CH:14]=[C:15]([CH3:17])[CH:16]=[C:8]([CH2:7][N:5]([CH2:4][CH2:3][O:2][CH3:1])[CH3:6])[CH:9]=1)[C@H:63]([OH:75])[CH2:64][NH:65][CH2:66][C:67]1[CH:72]=[CH:71][CH:70]=[C:69]([CH2:73][CH3:74])[CH:68]=1

Komponenten

7

Edukt 6

HCID 6344Dichloromethane2×HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210856713-{[(2-Methoxyethyl)(methyl)amino]methyl}-5-methylbenzoic AcidHCID 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

Produkt 1

HCID 68610692N-{(1S,2R)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[(2-methoxyethyl)(methyl)amino]methyl}-5-methylbenzamide Dihydrochloride

Versuchsvorschrift

To a stirred solution of 3-{[(2-methoxyethyl)(methyl)amino]methyl}-5-methylbenzoic acid (140 mg, 0.56 mmol) in methylene chloride (3 mL) is added HBTU (318 mg, 0.84 mmol), HOBt (114 mg, 0.84 mmol), and N,N-diisopropylethylamine (0.284 mL, 1.68 mmol), followed by (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol prepared by the method in EXAMPLE SP-272 (228 mg, 0.56 mmol). The reaction mixture is stirred for 24 h at room temperature, diluted with methylene chloride, washed with water, and saturated sodium bicarbonate, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 10% methanol/chloroform) affords the title compound as the free base. The compound is dissolved in methanol (2 mL), and to this solution is added hydrochloric acid (5 mL, 4 N dioxane, 20 mmol). The reaction mixture is stirred for 1 h at room temperature. The reaction mixture is then diluted with ethyl ether (10 mL). The precipitate that is formed is collected by filtration to provide the title compound. ESI MS m/z 554 [M+H]+.

Aufarbeitung

  1. washwashed with water, and saturated sodium bicarbonate
  2. dry with materialdried (magnesium sulfate)
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash column chromatography (silica, 10% methanol/chloroform)

Quellen und Nachweise

ORD-Eintrag
ord-bbc11ca5e72f4412b2dce029ffe97ff8
Quelldatensatz
uspto-grants-2007_02
Patentnummer
US07176242B2

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