Lithium Hexamethyldisilazide → HCID 66611412, Verbindung

HRID 1621841Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1621841
F[C:2]1[C:7]([C:8]2[N:13]=[C:12]([CH3:14])[N:11]=[C:10]([N:15]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=3)[CH2:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)[N:9]=2)=[CH:6][C:5]([C@H:34]([N:36]2[CH2:41][CH2:40][N:39]([S:42]([CH3:45])(=[O:44])=[O:43])[CH2:38][CH2:37]2)[CH3:35])=[CH:4][N:3]=1.[F:46][C:47]1[CH:56]=[C:55]([NH2:57])[CH:54]=[C:53]2[C:48]=1[CH:49]=[CH:50][CH:51]=[N:52]2.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1.[NH4+].[Cl-]>[CH3:24][O:23][C:20]1[CH:19]=[CH:18][C:17]([CH2:16][N:15]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[C:10]2[N:11]=[C:12]([CH3:14])[N:13]=[C:8]([C:7]3[C:2]([NH:57][C:55]4[CH:54]=[C:53]5[C:48]([CH:49]=[CH:50][CH:51]=[N:52]5)=[C:47]([F:46])[CH:56]=4)=[N:3][CH:4]=[C:5]([C@H:34]([N:36]4[CH2:41][CH2:40][N:39]([S:42]([CH3:45])(=[O:43])=[O:44])[CH2:38][CH2:37]4)[CH3:35])[CH:6]=3)[N:9]=2)=[CH:22][CH:21]=1

Komponenten

6

Edukt 3

HCID 2733832Lithium HexamethyldisilazideHCID 666002875-Fluoroquinolin-7-amineHCID 66611822(R)-4-(2-fluoro-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Produkt 1

HCID 66611412HCID 66611412, VerbindungAusbeute 71,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 25517Ammonium ChlorideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A mixture of (R)-4-(2-fluoro-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (Example 146, Step 6) (140 mg, 0.220 mmol), 5-fluoroquinolin-7-amine (35.7 mg, 0.220 mmol) and lithium bis(trimethylsilyl)amide (1.0 M in THF; 0.661 mL, 0.661 mmol, Aldrich) in THF (3 mL) was stirred at 0° C. for 1 h. The reaction mixture was diluted with saturated NH4Cl (10 mL) and extracted with EtOAc (2×30 mL). The organic extract was washed with saturated NaCl (10 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as yellow oil. The crude product was purified by silica gel chromatography eluting with EtOAc to give (R)—N-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-2-yl)-5-fluoroquinolin-7-amine (122 mg, 0.157 mmol, 71.2% yield). 1H NMR (300 MHz, CDCl3) δ 1.40 (d, J=6.72 Hz, 3H) 2.57 (dd, J=11.91, 4.17 Hz, 4H) 2.65 (s, 3H) 2.67 (s, 3H) 3.07-3.24 (m, 4H) 3.81 (s, 3H) 4.76-4.98 (m, 4H) 6.86 (dd, J=12.28, 8.62 Hz, 4H) 7.11-7.25 (m, 9H) 7.38-7.52 (m, 1H) 7.82 (d, J=8.48 Hz, 1H) 8.42 (d, J=2.19 Hz, 1H) 8.77 (d, J=2.34 Hz, 1H) 8.91 (d, J=2.49 Hz, 1H) 9.14 (d, J=2.05 Hz, 1H) 12.57 (s, 1H). m/z (ESI, +ve ion) 778.1 (M+H)+.

Aufarbeitung

  1. extractionextracted with EtOAc (2×30 mL)
  2. extractionThe organic extract
  3. washwas washed with saturated NaCl (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationThe solution was filtered
  6. concentrationconcentrated in vacuo
  7. customto give the crude material as yellow oil
  8. customThe crude product was purified by silica gel chromatography
  9. washeluting with EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-ac168172296943f3b9b1e5c0d696ce39
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08772480B2

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