Lithium Hexamethyldisilazide → 7-chloro-N-(3-cyclopropyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 79405Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 79405
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]([O:13]CC)=O)=[CH:9][N:10]=[C:4]2[CH:3]=1.[CH:16]1([C:19]2[C:27]3[C:26]([NH2:28])=[CH:25][CH:24]=[CH:23][C:22]=3[N:21]([CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([CH3:36])[N:31]=3)[N:20]=2)[CH2:18][CH2:17]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1.CC(O)C>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]([NH:28][C:26]3[CH:25]=[CH:24][CH:23]=[C:22]4[C:27]=3[C:19]([CH:16]3[CH2:18][CH2:17]3)=[N:20][N:21]4[CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([CH3:36])[N:31]=3)=[O:13])=[CH:9][N:10]=[C:4]2[CH:3]=1

Komponenten

6

Edukt 3

HCID 2733832Lithium HexamethyldisilazideHCID 67107280Ethyl 7-chloroimidazo[1,2-A]pyridine-3-carboxylateHCID 672592723-cyclopropyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazole-4-amine

Produkt 1

HCID 672599697-chloro-N-(3-cyclopropyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamideAusbeute 90,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3776IsopropanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A mixture of ethyl 7-chloroimidazo[1,2-a]pyridine-3-carboxylate (10.0 g, 44.5 mmol) and 3-cyclopropyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-amine (12.4 g, 44.5 mmol) in THF (100 mL) was cooled to 0° C. using an ice/water bath. A solution of 1.0M lithium bis(trimethylsilyl)amide (102 mL, 102 mmol) was added slowly over 40 minutes keeping the internal temperature below 5° C. The mixture was stirred at 0° C. for 30 minutes, diluted with IPA (100 mL), and then concentrated under reduced pressure. The residue was diluted with IPA (100 mL) and concentrated under reduced pressure. The residue was dissolved in IPA (100 mL) and treated with a 10% aqueous ammonium chloride solution (200 mL) to give a slurry which was filtered and dried to give 7-chloro-N-(3-cyclopropyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide as a light brown solid (18.4 g).

Aufarbeitung

  1. customthe internal temperature below 5° C
  2. concentrationconcentrated under reduced pressure
  3. additionThe residue was diluted with IPA (100 mL)
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in IPA (100 mL)
  6. additiontreated with a 10% aqueous ammonium chloride solution (200 mL)
  7. customto give a slurry which
  8. filtrationwas filtered
  9. customdried

Quellen und Nachweise

ORD-Eintrag
ord-9a1a8e609eaa46d9a3e16cf252fb8b17
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08841455B2

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