Bis(2-oxo-3-oxazolidinyl)phosphinic chloride → 1h-Pyrrolo[3,2-b]pyridine-2-carboxamide,1-[[5-(5-chloro-2-thienyl)-3-isoxazolyl]methyl]-n-[1-(1-methylethyl)-4-piperidinyl]-

HRID 2250433

Reaktionsgleichung

Reaktionsgleichung von HRID 2250433
[Cl:1][C:2]1[S:6][C:5]([C:7]2[O:11][N:10]=[C:9]([CH2:12][N:13]3[C:21]4[C:16](=[N:17][CH:18]=[CH:19][CH:20]=4)[CH:15]=[C:14]3[C:22](O)=[O:23])[CH:8]=2)=[CH:4][CH:3]=1.Cl.[CH:26]([N:29]1[CH2:34][CH2:33][CH:32]([NH2:35])[CH2:31][CH2:30]1)([CH3:28])[CH3:27].O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1>ClCCl.C(N(CC)CC)C>[CH:26]([N:29]1[CH2:34][CH2:33][CH:32]([NH:35][C:22]([C:14]2[N:13]([CH2:12][C:9]3[CH:8]=[C:7]([C:5]4[S:6][C:2]([Cl:1])=[CH:3][CH:4]=4)[O:11][N:10]=3)[C:21]3[C:16](=[N:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=2)=[O:23])[CH2:31][CH2:30]1)([CH3:28])[CH3:27]

Komponenten

6

Edukt 3

HCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 230334601-Isopropylpiperidin-4-amine hydrochlorideHCID 692269921h-Pyrrolo[3,2-b]pyridine-2-carboxylic acid,1-[[5-(5-chloro-2-thienyl)-3-isoxazolyl]methyl]-

Produkt 1

HCID 99131941h-Pyrrolo[3,2-b]pyridine-2-carboxamide,1-[[5-(5-chloro-2-thienyl)-3-isoxazolyl]methyl]-n-[1-(1-methylethyl)-4-piperidinyl]-

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

To a suspension of 50 mg 1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrrolo[3,2-b]pyridine-2-carboxylic acid, 36 mg 1-isopropyl-piperidin-4-ylamine hydrochloride and 35 mg bis(2-oxo-3-oxazolidinyl)phosphinic chloride in 1 mL dichloromethane, 77 μl triethylamine were added at room temperature and the mixture was stirred for 16 hours. After removing of the solvent under reduced pressure, the residue was purified by preparative HPLC (C18 reverse phase column, elution with a water/acetonitrile gradient with 0.1% trifluoroacetic acid). The fractions containing the product were evaporated and lyophilized to yield a white residue which was partitioned between 5 mL aqueous 0.1 N sodium hydroxide solution and 5 mL ethyl acetate. The organic layer was washed with additional water and then dried over sodium sulphate. After filtration and removal of the solvent under reduced pressure, a white solid was obtained.

Aufarbeitung

  1. additionwere added at room temperature
  2. customAfter removing of the solvent under reduced pressure
  3. customthe residue was purified by preparative HPLC (
  4. washC18 reverse phase column, elution with a water/acetonitrile gradient with 0.1% trifluoroacetic acid)
  5. additionThe fractions containing the product
  6. customwere evaporated
  7. customto yield a white residue which
  8. customwas partitioned between 5 mL aqueous 0.1 N sodium hydroxide solution and 5 mL ethyl acetate
  9. washThe organic layer was washed with additional water
  10. dry with materialdried over sodium sulphate
  11. filtrationAfter filtration and removal of the solvent under reduced pressure
  12. customa white solid was obtained

Quellen und Nachweise

ORD-Eintrag
ord-f954f163e0ed4341b8c473ef5f16f735
Quelldatensatz
uspto-grants-2008_01
Patentnummer
US07317027B2

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