Lithium Hexamethyldisilazide → HCID 59548448, Verbindung

HRID 1621786

Reaktionsgleichung

Reaktionsgleichung von HRID 1621786
[NH2:1][C:2]1[CH:3]=[C:4]([NH:9][S:10]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)(=[O:12])=[O:11])[C:5]([Cl:8])=[N:6][CH:7]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].F[C:31]1[C:36]([C:37]2[N:42]=[C:41]([CH3:43])[N:40]=[C:39]([NH2:44])[N:38]=2)=[CH:35][CH:34]=[CH:33][N:32]=1>C1COCC1>[NH2:44][C:39]1[N:40]=[C:41]([CH3:43])[N:42]=[C:37]([C:36]2[C:31]([NH:1][C:2]3[CH:3]=[C:4]([NH:9][S:10]([C:13]4[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=4)(=[O:11])=[O:12])[C:5]([Cl:8])=[N:6][CH:7]=3)=[N:32][CH:33]=[CH:34][CH:35]=2)[N:38]=1

Komponenten

5

Edukt 3

HCID 2733832Lithium HexamethyldisilazideHCID 665998524-(2-Fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amineHCID 71480919N-(5-amino-2-chloropyridin-3-yl)-4-fluorobenzenesulfonamide

Produkt 1

HCID 59548448HCID 59548448, VerbindungAusbeute 30,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A solution of N-(5-amino-2-chloropyridin-3-yl)-4-fluorobenzenesulfonamide (0.124 g, 0.409 mmol) in THF (5 mL) was cooled to 0° C. under N2. Lithium bis(trimethylsilyl)amide, 1.0 M solution in tetrahydrofuran (Aldrich) (1.706 mL, 1.706 mmol) was added dropwise and the mixture was stirred at 0° C. for 30 min. 4-(2-Fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.070 g, 0.341 mmol) was added and the mixture was stirred at 0° C. for 10 min. The reaction mixture was then stirred at rt for 20 h. The reaction was quenched with sat. NH4Cl and the resulting mixture was partitioned between sat. NaHCO3 and CHCl3. The aqueous layer was extracted with CHCl3 (2×15 mL). The combined organic layers were dried over MgSO4 and concentrated. The crude product was purified by prep HPLC. Fractions containing the product were combined and concentrated. The residue was basified using sat. NaHCO3 (10 mL). The aqueous layer was extracted with CHCl3 (3×15 mL). The combined organic layers were dried over MgSO4 and concentrated to give the product as a yellow solid (0.050 g). m/z (ESI, +ve ion) 486.8 (M+H)+. 1H NMR (300 MHz, CDCl3) δ 12.38 (s, 1H); 8.74-9.01 (m, 2H); 8.44 (d, J=3.22 Hz, 1H); 8.39 (d, J=2.34 Hz, 1H); 7.95 (dd, J=8.62, 5.12 Hz, 2H); 7.15 (t, J=8.48 Hz, 2H); 6.86-7.03 (m, 2H); 5.43 (br. s., 2H); 2.60 (s, 3H).

Aufarbeitung

  1. stirringthe mixture was stirred at 0° C. for 10 min
  2. stirringThe reaction mixture was then stirred at rt for 20 h
  3. customThe reaction was quenched with sat. NH4Cl
  4. customthe resulting mixture was partitioned between sat. NaHCO3 and CHCl3
  5. extractionThe aqueous layer was extracted with CHCl3 (2×15 mL)
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. concentrationconcentrated
  8. customThe crude product was purified by prep HPLC
  9. additionFractions containing the product
  10. concentrationconcentrated
  11. extractionThe aqueous layer was extracted with CHCl3 (3×15 mL)
  12. dry with materialThe combined organic layers were dried over MgSO4
  13. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-60271a30040e488fbcda40796f94fbcb
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08772480B2

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