Tetrahydrofuran → 2-[2-Amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]-N-(6-methylpyridin-2-yl)-1,2,3,4-tetrahydroisoquinolin-7-amine

HRID 2090299Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2090299
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][N:8]([C:12]3[CH:17]=[C:16]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[N:15]=[C:14]([NH2:25])[N:13]=3)[CH2:9]2)=[CH:4][CH:3]=1.[CH3:26][C:27]1[N:32]=[C:31]([NH2:33])[CH:30]=[CH:29][CH:28]=1.CC(C)([O-])C.[K+].O1CCCC1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:25][C:14]1[N:13]=[C:12]([N:8]2[CH2:7][CH2:6][C:5]3[C:10](=[CH:11][C:2]([NH:33][C:31]4[CH:30]=[CH:29][CH:28]=[C:27]([CH3:26])[N:32]=4)=[CH:3][CH:4]=3)[CH2:9]2)[CH:17]=[C:16]([N:18]2[CH2:19][CH2:20][N:21]([CH3:24])[CH2:22][CH2:23]2)[N:15]=1

Komponenten

7

Edukt 5

HCID 8028TetrahydrofuranHCID 157652-Amino-6-methylpyridineHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 23665647Potassium tert-butoxideHCID 467010484-(7-bromo-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine

Produkt 1

HCID 467012542-[2-Amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]-N-(6-methylpyridin-2-yl)-1,2,3,4-tetrahydroisoquinolin-7-amine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 167845palladium(II) acetateLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A mixture of 4-(7-bromo-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine (20.0 mg, 0.0496 mmol), 6-methyl-2-pyridinamine, (8.04 mg, 0.0744 mmol, Aldrich, Cat. No. A75706), a solution of potassium tert-butoxide in tetrahydrofuran (0.0992 mL, 0.0992 mmol, 1.00 M, Aldrich Cat. 328650), palladium acetate (0.445 mg, 0.00198 mmol, Aldrich, Cat. No. 379875), and 2-[dicyclohexylphosphino]biphenyl (0.869 mg, 0.00248 mmol, Aldrich, Cat. No. 638099) in 1,4-dioxane (1 mL) was degassed with nitrogen and then heated at 120° C. for 16 hours. The reaction mixture was cooled to r.t. and concentrated. Then the reaction mixture was dissolved in MeOH and purified by RP-HPLC (pH=10) to afford the desired compound. LCMS(M+H)+: m/z=431.4.

Aufarbeitung

  1. custom638099) in 1,4-dioxane (1 mL) was degassed with nitrogen
  2. temperatureThe reaction mixture was cooled to r.t.
  3. concentrationconcentrated
  4. dissolutionThen the reaction mixture was dissolved in MeOH
  5. custompurified by RP-HPLC (pH=10)

Quellen und Nachweise

ORD-Eintrag
ord-4faee5b912fc4e5b9e1fe5bebdcfbef2
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08436008B2

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