Chloroform → 6-{[3-chloro-5-(2,2-diethoxyethyl)pyridin-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amine

HRID 1517259

Reaktionsgleichung

Reaktionsgleichung von HRID 1517259
[Cl:1][C:2]1[C:7](Cl)=[CH:6][C:5]([O:9][CH2:10][CH:11]([O:15][CH2:16][CH3:17])[O:12][CH2:13][CH3:14])=[CH:4][N:3]=1.C[C:19]([CH3:22])([O-])C.[K+].[CH3:24][N:25](C)[C:26](=[O:28])[CH3:27].[CH3:30][N:31]1[CH:35]=[CH:34][C:33]([NH:36][C:37]2[C:46]3[C:41](=[CH:42][CH:43]=[C:44]([OH:47])[CH:45]=3)[N:40]=[CH:39][N:38]=2)=[N:32]1.C(Cl)(Cl)[Cl:49]>O>[Cl:49][C:27]1[C:26]([O:28][C:44]2[CH:45]=[C:46]3[C:41](=[CH:42][CH:43]=2)[N:40]=[CH:39][N:38]=[C:37]3[NH:36][C:33]2[CH:34]=[CH:35][N:31]([CH3:30])[N:32]=2)=[N:25][CH:24]=[C:19]([CH2:10][CH:11]([O:12][CH2:13][CH3:14])[O:15][CH2:16][CH3:17])[CH:22]=1.[Cl:1][C:2]1[C:7]([O:47][C:44]2[CH:45]=[C:46]3[C:41](=[CH:42][CH:43]=2)[N:40]=[CH:39][N:38]=[C:37]3[NH:36][C:33]2[CH:34]=[CH:35][N:31]([CH3:30])[N:32]=2)=[CH:6][C:5]([O:9][CH2:10][CH:11]([O:15][CH2:16][CH3:17])[O:12][CH2:13][CH3:14])=[CH:4][N:3]=1

Komponenten

8

Edukt 5

HCID 6212ChloroformHCID 31374DimethylacetamideHCID 231603824-[(1-Methyl-1H-pyrazol-3-yl)amino]quinazolin-6-olHCID 23665647Potassium tert-butoxideHCID 866458962,3-Dichloro-5-(2,2-diethoxyethoxy)pyridine

Produkt 2

HCID 684277006-{[3-chloro-5-(2,2-diethoxyethyl)pyridin-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amineAusbeute 45 %HCID 866458956-{[2-chloro-5-(2,2-diethoxyethoxy)pyridin-3-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amineAusbeute 28 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
170 °C

Versuchsvorschrift

2,3-Dichloro-5-(2,2-diethoxyethoxy)pyridine (641 mg, 2.29 mmol) and potassium tert-butoxide (279 mg, 2.49 mmol) were added to an N,N-dimethylacetamide solution (3 ml) of 4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-ol (240 mg, 1.00 mmol), and stirred at 170° C. for 14 hours under a nitrogen atmosphere in a sealed tube. The reaction solution was cooled with ice, then saline water and chloroform were added, the organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by reversed-phase liquid chromatography (YMC CombiPrep Pro C18 AS-360-CC) to obtain 6-{[3-chloro-5-(2,2-diethoxyethyl)pyridin-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amine (217 mg, yield: 45%) as an orange oil and 6-{[2-chloro-5-(2,2-diethoxyethoxy)pyridin-3-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)quinazoline-4-amine (136 mg, yield: 28%) as an orange oil.

Aufarbeitung

  1. temperatureThe reaction solution was cooled with ice
  2. washthe organic layer was washed with water
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe obtained residue was purified by reversed-phase liquid chromatography (YMC CombiPrep Pro C18 AS-360-CC)

Quellen und Nachweise

ORD-Eintrag
ord-b1e3fb08da3c46749af94e3278812389
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08232284B2

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