2-(5-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-2-morpholinopropanenitrile → 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-(2-morpholinopropan-2-yl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

HRID 1621821Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1621821
[CH3:1][O:2][C:3]1[CH:52]=[CH:51][C:6]([CH2:7][N:8]([CH2:42][C:43]2[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][CH:44]=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[CH:17]=[C:18]([C:32]([N:36]4[CH2:41][CH2:40][O:39][CH2:38][CH2:37]4)([CH3:35])[C:33]#N)[CH:19]=[N:20][C:21]=3[NH:22][C:23]3[CH:24]=[N:25][C:26]([O:30][CH3:31])=[C:27]([F:29])[CH:28]=3)[N:10]=2)=[CH:5][CH:4]=1.C[Mg]Br>C1COCC1>[F:29][C:27]1[CH:28]=[C:23]([NH:22][C:21]2[C:16]([C:11]3[N:12]=[C:13]([CH3:15])[N:14]=[C:9]([N:8]([CH2:7][C:6]4[CH:51]=[CH:52][C:3]([O:2][CH3:1])=[CH:4][CH:5]=4)[CH2:42][C:43]4[CH:44]=[CH:45][C:46]([O:49][CH3:50])=[CH:47][CH:48]=4)[N:10]=3)=[CH:17][C:18]([C:32]([N:36]3[CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)([CH3:33])[CH3:35])=[CH:19][N:20]=2)[CH:24]=[N:25][C:26]=1[O:30][CH3:31]

Komponenten

4

Edukt 2

HCID 666114652-(5-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-2-morpholinopropanenitrileHCID 178418573HCID 178418573, Verbindung

Produkt 1

HCID 666111624-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-(2-morpholinopropan-2-yl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineAusbeute 73,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A solution of 2-(5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-2-morpholinopropanenitrile (0.500 g, 0.708 mmol) in THF (2 mL) at 0° C. was treated with methylmagnesium bromide (3.0 M in diethyl ether; 1.181 mL, 3.54 mmol). The cooling bath was removed after 10 min, and the reaction was allowed to warm to ambient temperature. After 2 h total, the reaction was cooled to 0° C. and quenched with EtOAc (1 mL) followed by ice and sat'd aq. NH4Cl. The reaction was partitioned between satd NH4Cl and DCM. The aqueous layer was extracted with DCM (3×) and the combined organic extracts were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The material was treated with DCM and purified by silica gel chromatography using 10-80% EtOAc/hexane. The product-containing fractions were concentrated to give 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-(2-morpholinopropan-2-yl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.363 g, 0.522 mmol, 73.7% yield) as a yellow solid. m/z (ESI, +ve ion) 695 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 11.86 (s, 1H); 8.96 (d, J=2.5 Hz, 1H); 8.47 (d, J=2.5 Hz, 1H); 8.13 (dd, J=12.5, 2.2Hz, 1H); 7.91-8.01 (m, 1H); 7.17-7.26 (m, 4H); 6.75-6.96 (m, 4H); 4.89 (s, 2H); 4.84 (s, 2H); 4.02 (s, 3H); 3.82 (s, 3H); 3.79 (s, 3H); 3.55-3.65 (m, 4H); 2.59 (s, 3H); 2.42-2.51 (m, 4H); 1.35 (s, 6H).

Aufarbeitung

  1. customThe cooling bath was removed after 10 min
  2. temperaturethe reaction was cooled to 0° C.
  3. customquenched with EtOAc (1 mL)
  4. customThe reaction was partitioned between satd NH4Cl and DCM
  5. extractionThe aqueous layer was extracted with DCM (3×)
  6. dry with materialthe combined organic extracts were dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. additionThe material was treated with DCM
  10. custompurified by silica gel chromatography
  11. concentrationThe product-containing fractions were concentrated

Quellen und Nachweise

ORD-Eintrag
ord-1d67853908f24ba38e593fc4a9f400bf
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08772480B2

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