Diisopropylethylamine → 1-(2,3-Dihydroxypropoxy)-4-[(4-{[1-methoxy-3-(methylamino)-1,3-dioxopropan-2-yl](methyl)carbamoyl}phenyl)ethynyl]benzene

HRID 1519690Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1519690
Cl.[CH3:2][NH:3][C:4](=[O:12])[C@H:5]([C:8](=[O:11])[O:9][CH3:10])[NH:6][CH3:7].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[OH:46][CH:47]([CH2:67][OH:68])[CH2:48][O:49][C:50]1[CH:55]=[CH:54][C:53]([C:56]#[C:57][C:58]2[CH:66]=[CH:65][C:61]([C:62]([OH:64])=O)=[CH:60][CH:59]=2)=[CH:52][CH:51]=1.C(=O)([O-])O.[Na+]>CN(C=O)C>[OH:46][CH:47]([CH2:67][OH:68])[CH2:48][O:49][C:50]1[CH:51]=[CH:52][C:53]([C:56]#[C:57][C:58]2[CH:59]=[CH:60][C:61]([C:62](=[O:64])[N:6]([CH:5]([C:4]([NH:3][CH3:2])=[O:12])[C:8]([O:9][CH3:10])=[O:11])[CH3:7])=[CH:65][CH:66]=2)=[CH:54][CH:55]=1

Komponenten

7

Edukt 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712681454-{[4-(2,3-Dihydroxypropoxy)phenyl]ethynyl}benzoic acidHCID 86679246N,N2,O-trimethyl-3-oxoserinamide hydrochloride2×

Produkt 1

HCID 712681471-(2,3-Dihydroxypropoxy)-4-[(4-{[1-methoxy-3-(methylamino)-1,3-dioxopropan-2-yl](methyl)carbamoyl}phenyl)ethynyl]benzeneAusbeute 8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

N,N2,O-trimethyl-3-oxoserinamide hydrochloride (Intermediate 5-2, 0.13 g), HATU (0.17 g) and DIPEA (0.33 mL) were added to a DMF (2.0 mL) solution of 4-{[4-(2,3-dihydroxypropoxy)phenyl]ethynyl}benzoic acid (0.20 g) as obtained in Example 11-(2), and the mixture was stirred for 1 hour at 80° C. A saturated aqueous solution of sodium hydrogen carbonate was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was washed with brine, and dried over anhydrous magnesium sulfate. The desiccant was filtered out, and the solvent was distilled off under reduced pressure. The resulting residue was purified by NH type silica gel column chromatography (gradient elution with ethyl acetate/methanol=99/1→88/12) to obtain 1-(2,3-dihydroxypropoxy)-4-[(4-{[1-methoxy-3-(methylamino)-1,3-dioxopropan-2-yl](methyl)carbamoyl}phenyl)ethynyl]benzene (white solid) (23 mg, 8.0%).

Aufarbeitung

  1. customas obtained in Example 11-(2)
  2. extractionthe mixture was extracted with chloroform
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationThe desiccant was filtered out
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe resulting residue was purified by NH type silica gel column chromatography (gradient elution with ethyl acetate/methanol=99/1→88/12)

Quellen und Nachweise

ORD-Eintrag
ord-ef11bf582d124167b227aa3e6c5e1432
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09073821B2

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