Bis(2-oxo-3-oxazolidinyl)phosphinic chloride → {3-chloro-2-hydroxy-5-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-[4-(2-diethylamino-ethyl)-piperazin-1-yl]-methanone

HRID 1865627Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1865627
[Cl:1][C:2]1[C:3]([OH:28])=[C:4]([CH:8]=[C:9]([C:11]2[CH:12]=[C:13]3[C:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[O:26][CH3:27])=[N:18][NH:17][C:14]3=[N:15][CH:16]=2)[CH:10]=1)[C:5]([OH:7])=O.[CH2:29]([N:31]([CH2:40][CH3:41])[CH2:32][CH2:33][N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1)[CH3:30].O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.C(=O)(O)[O-].[Na+]>C(#N)C.CN(C=O)C.O.C(OCC)(=O)C>[Cl:1][C:2]1[C:3]([OH:28])=[C:4]([C:5]([N:37]2[CH2:38][CH2:39][N:34]([CH2:33][CH2:32][N:31]([CH2:40][CH3:41])[CH2:29][CH3:30])[CH2:35][CH2:36]2)=[O:7])[CH:8]=[C:9]([C:11]2[CH:12]=[C:13]3[C:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[O:26][CH3:27])=[N:18][NH:17][C:14]3=[N:15][CH:16]=2)[CH:10]=1

Komponenten

9

Edukt 4

HCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chloride2×HCID 516892Sodium BicarbonateHCID 2736105N,N-Diethyl-2-(piperazin-1-yl)ethan-1-amineHCID 1784893953-chloro-2-hydroxy-5-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-benzoic acid

Produkt 1

HCID 178464031{3-chloro-2-hydroxy-5-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-[4-(2-diethylamino-ethyl)-piperazin-1-yl]-methanoneAusbeute 17 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

14 mg (35 mol) of 3-chloro-2-hydroxy-5-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-benzoic acid and 22 μL (approx. 120 μmol; density unknown) of 1-(2-diethylaminoethyl)-piperazine were dissolved in a mixture of 1 mL of acetonitrile and 100 μL of DMF. 14 mg (55 μmol) of bis(2-oxo-3-oxazolidinyl)phosphinic chloride was added and the mixture heated gently until all materials were dissolved. The resulting solution was left at ambient temperature for 4.5 h. 28 mg (110 μmol) of bis(2-oxo-3-oxazolidinyl)phosphinic chloride was added and the resulting mixture left at ambient temperature for 3.5 h, then heated to 75° C. for 3.5 h. The resulting mixture was distributed between 1 mL of a saturated aqueous solution of sodium bicarbonate in water and 2 mL of ethyl acetate. The organic phase was evaporated and the residue directly purified by mass-triggered reverse-phase HPLC to afford 3.2 mg (5.7 μmol, 17%) of {3-chloro-2-hydroxy-5-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-[4-(2-diethylamino-ethyl)-piperazin-1-yl]-methanone as an off-white solid. 1H NMR (500 MHz, DMSO-d6) δ 13.80 (s, br. 1H), 8.81 (d, 1H), 8.29 (d, 1H), 7.82 (d, 1H), 7.64 (dd, 1H), 7.49-7.44 (m, 2H), 7.21 (d, 1H), 7.10 (ddd, 1H), 3.83 (s, 3H), 3.40-3.30 (m, 4H), 2.49-2.35 (m, 8H), 0.94 (t, 6H), MS: m/z 563.2 (M+H+).

Aufarbeitung

  1. temperaturethe mixture heated gently until all materials
  2. dissolutionwere dissolved
  3. waitthe resulting mixture left at ambient temperature for 3.5 h
  4. customThe organic phase was evaporated
  5. customthe residue directly purified by mass-triggered reverse-phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-d85e36c0aaf64f72a99fdf84dd29896a
Quelldatensatz
uspto-grants-2009_12
Patentnummer
US07626021B2

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