Dichloromethane → 4-[3-methyl-7-(2-methyl-1,3-thiazol-4-yl)-3,4-dihydroisoquinolin-2(1H)-yl]-6-(4-methylpiperazin-1-yl) pyrimidin-2-amine

HRID 2090452Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2090452
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[C:12]([N:14]3[CH:23]([CH3:24])[CH2:22][C:21]4[C:16](=[CH:17][C:18](B5OC(C)(C)C(C)(C)O5)=[CH:19][CH:20]=4)[CH2:15]3)[N:11]=[C:10]([NH2:34])[N:9]=2)[CH2:4][CH2:3]1.Br[C:36]1[N:37]=[C:38]([CH3:41])[S:39][CH:40]=1.C(=O)([O-])[O-].[K+].[K+].ClCCl>O1CCOCC1.O>[CH3:24][CH:23]1[CH2:22][C:21]2[C:16](=[CH:17][C:18]([C:36]3[N:37]=[C:38]([CH3:41])[S:39][CH:40]=3)=[CH:19][CH:20]=2)[CH2:15][N:14]1[C:12]1[CH:13]=[C:8]([N:5]2[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]2)[N:9]=[C:10]([NH2:34])[N:11]=1

Komponenten

7

Edukt 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 27631864-Bromo-2-methyl-1,3-thiazoleHCID 594022564-(4-methylpiperazin-1-yl)-6-[3-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinolin-2(1H)-yl]pyrimidin-2-amine

Produkt 1

HCID 467019184-[3-methyl-7-(2-methyl-1,3-thiazol-4-yl)-3,4-dihydroisoquinolin-2(1H)-yl]-6-(4-methylpiperazin-1-yl) pyrimidin-2-amine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A mixture of 4-(4-methylpiperazin-1-yl)-6-[3-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinolin-2(1H)-yl]pyrimidin-2-amine (0.0464 g, 0.100 mmol), 4-bromo-2-methyl-1,3-thiazole (0.0231 g, 0.130 mmol, Frontier, Cat. No. B4559) in 1,4-dioxane (1.0 mL) was stirred at r.t. for 10 min. Potassium carbonate (63.0 mg, 0.456 mmol) in water (0.50 mL) was added to give a deep red solution. The mixture was degassed and refilled with nitrogen three times. [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (5.0 mg, 0.0061 mmol) was added and the mixture was degassed and refilled with nitrogen three times and then heated at 120° C.) (oil bath temperature) for 3 h. After cooling, the mixture was diluted with methanol, and filtered. The filtrate was purified on RP-HPLC (pH=10) to afford the desired product. LCMS (M+H)+: m/z=436.1.

Aufarbeitung

  1. customto give a deep red solution
  2. customThe mixture was degassed
  3. additionrefilled with nitrogen three times
  4. customthe mixture was degassed
  5. additionrefilled with nitrogen three times
  6. temperatureAfter cooling
  7. additionthe mixture was diluted with methanol
  8. filtrationfiltered
  9. customThe filtrate was purified on RP-HPLC (pH=10)

Quellen und Nachweise

ORD-Eintrag
ord-78395596a7344c71ad6a6d56089072f7
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08436008B2

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