Sodium bis(trimethylsilyl)amide → N'-(5-((3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(4-morpholinylmethyl)-2-pyridinyl)amino)-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide

HRID 1812358

Reaktionsgleichung

Reaktionsgleichung von HRID 1812358
F[C:2]1[C:7]([C:8]2[N:13]=[C:12]([CH3:14])[N:11]=[C:10]([NH2:15])[N:9]=2)=[CH:6][C:5]([CH2:16][N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[CH:4][N:3]=1.[NH2:23][C:24]1[CH:25]=[C:26]([NH:31][S:32]([N:35]([CH3:37])[CH3:36])(=[O:34])=[O:33])[C:27]([Cl:30])=[N:28][CH:29]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>CN(C=O)C>[NH2:15][C:10]1[N:11]=[C:12]([CH3:14])[N:13]=[C:8]([C:7]2[C:2]([NH:23][C:24]3[CH:25]=[C:26]([NH:31][S:32]([N:35]([CH3:37])[CH3:36])(=[O:33])=[O:34])[C:27]([Cl:30])=[N:28][CH:29]=3)=[N:3][CH:4]=[C:5]([CH2:16][N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[CH:6]=2)[N:9]=1

Komponenten

5

Edukt 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 66611272HCID 66611272, VerbindungHCID 71480922N'-(5-amino-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide

Produkt 1

HCID 59548260N'-(5-((3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(4-morpholinylmethyl)-2-pyridinyl)amino)-2-chloro-3-pyridinyl)-N,N-dimethylsulfamideAusbeute 44 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a stirred solution of 4-(2-fluoro-5-(morpholinomethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (Example 384, Step 2, 0.0614 g, 0.202 mmol) and N′-(5-amino-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide (KY, 0.050 g, 0.199 mmol) in DMF (1 mL) in 5 mL microwave vial, NaHMDS (Aldrich, 1 M in THF, 0.80 mL, 0.80 mmol) was added dropwise at 0° C. The mixture was stirred at 0° C. for 45 min. The reaction mixture was partitioned between saturated aqueous ammonium chloride (30 mL) and 25% isopropanol in chloroform (20 mL). The aqueous phase was acidified to a pH of about 3 to 4 then extracted with 25% isopropanol in chloroform (2×30 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography (25 g, eluent: iPrOH in CHCl3 0%-25%) to afford N′-(5-((3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(4-morpholinylmethyl)-2-pyridinyl)amino)-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide (0.0437 g, 44% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.28 (s, 1H) 9.57 (s, 1H) 8.82 (s, 1H) 8.76 (d, J=2.35 Hz, 1H) 8.53 (d, J=2.35 Hz, 1H) 8.29 (d, J=2.35 Hz, 1H) 7.74-7.98 (m, 2H) 3.57 (t, J=4.21 Hz, 4H) 3.48 (s, 2H) 2.79 (s, 6H) 2.46 (s, 3H) 2.35-2.43 (m, 4H). m/z (ESI, positive ion): 535.0 (M+H)+.

Aufarbeitung

  1. customThe reaction mixture was partitioned between saturated aqueous ammonium chloride (30 mL) and 25% isopropanol in chloroform (20 mL)
  2. extractionthen extracted with 25% isopropanol in chloroform (2×30 mL)
  3. dry with materialThe combined organic phases were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by silica gel column chromatography (25 g, eluent: iPrOH in CHCl3 0%-25%)

Quellen und Nachweise

ORD-Eintrag
ord-3917e66da98147269a4acecf18a4766b
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08362241B2

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