Sodium Carbonate → [2-(3-Methylphenyl)-quinazolin-4-yl]-(5-methyl-2H-pyrazol-3-yl)-amine

HRID 38184

Reaktionsgleichung

Reaktionsgleichung von HRID 38184
Cl[C:2]1[N:11]=[C:10]([NH:12][C:13]2[CH:17]=[C:16]([CH3:18])[NH:15][N:14]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[C:19]1([CH3:28])[CH:24]=[CH:23][CH:22]=[C:21](B(O)O)[CH:20]=1.C([O-])([O-])=O.[Na+].[Na+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>CN(C=O)C.Cl[Pd]Cl.O>[CH3:28][C:19]1[CH:20]=[C:21]([C:2]2[N:11]=[C:10]([NH:12][C:13]3[NH:14][N:15]=[C:16]([CH3:18])[CH:17]=3)[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]=2)[CH:22]=[CH:23][CH:24]=1

Komponenten

8

Edukt 4

HCID 10340Sodium CarbonateHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 27339503-Tolylboronic acidHCID 219391632-Chloro-n-(5-methyl-1h-pyrazol-3-yl)quinazolin-4-amine

Produkt 1

HCID 178419088[2-(3-Methylphenyl)-quinazolin-4-yl]-(5-methyl-2H-pyrazol-3-yl)-amineAusbeute 101,8 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24290Palladium ChlorideKatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A suspension of 1H-quinazoline-2,4-dione (10.0 g, 61.7 mmol) in POCl3 (60 mL, 644 mmol) and N,N-dimethylaniline (8 mL, 63.1 mmol) was heated under reflux for 2 h. The excess POCl3 was removed in vacuo, the residue poured into ice, and the resulting precipitate collected by filtration. The crude solid product 2,4-dichloro-quinazoline (6.5 g, 53% yield) was washed with water and dried under vacuum for next step use without further purification. To a solution of the 2,4-dichloro-quinazoline (3.3 g, 16.6 mmol) in anhydrous ethanol (150 mL) was added 5-methyl-1H-pyrazol-3-yl amine (3.2 g, 32.9 mmol) and the resulting mixture was stirred at room temperature for 4 hours. The resulting precipitate was collected by filtration, washed with ethanol, and dried under vacuum to afford 4.0 g (93% yield) of (2-chloro-quinazolin-4-yl)-(5-methyl-1H-pyrazol-3-yl)-amine which was used in the next step without further purification. To a solution of the (2-chloro-quinazolin-4-yl)-(5-methyl-1H-pyrazol-3-yl)-amine (50 mg, 0.19 mmol) in DMF (1.0 mL) was added m-tolyl boronic acid (0.38 mmol), 2M Na2CO3 (0.96 mmol), and tri-t-butylphosphine (0.19 mmol). The flask was flushed with nitrogen and the catalyst PdCl2 (dppf) (0.011 mmol) added in one portion. The reaction mixture was then heated at 80° C. for 10 hours, cooled to room temperature, and poured into water (2 mL). The resulting precipitate was collected by filtration, washed with water, and purified by HPLC to afford III-50 as a pale yellow solid (61 mg, 75%): 1H NMR (500 MHz, DMSO-d6) δ 12.3 (br s, 1H), 10.4 (br s, 1H), 8.75 (d, 1H), 8.30 (s, 1H), 8.25 (d, 1H), 7.78 (s, 2H), 7.55 (m, 1H), 7.45 (m, 1H), 7.35 (m, 1H), 6.80 (s, 1H), 2.47 (s, 3H), 2.30 (s, 3H); MS 316.1 (M+H).

Aufarbeitung

  1. customwas used in the next step without further purification
  2. customThe flask was flushed with nitrogen
  3. temperaturecooled to room temperature
  4. filtrationThe resulting precipitate was collected by filtration
  5. washwashed with water
  6. custompurified by HPLC

Quellen und Nachweise

ORD-Eintrag
ord-8fc7862835724e3c9609f9877536f04e
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08524720B2

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