4-Iodo-o-toluidine → 3-[(2-Methyl-4-iodophenyl)amino]isonicotinic acid

HRID 39501

Reaktionsgleichung

Reaktionsgleichung von HRID 39501
[I:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([CH3:9])[CH:3]=1.F[C:11]1[CH:12]=[N:13][CH:14]=[CH:15][C:16]=1[C:17]([OH:19])=[O:18].[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[I:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:15]2[CH:14]=[N:13][CH:12]=[CH:11][C:16]=2[C:17]([OH:19])=[O:18])=[C:4]([CH3:9])[CH:3]=1

Komponenten

5

Edukt 3

HCID 832214-Iodo-o-toluidineHCID 3453613-Fluoropyridine-4-carboxylic acidHCID 2733832Lithium Hexamethyldisilazide

Produkt 1

HCID 576496173-[(2-Methyl-4-iodophenyl)amino]isonicotinic acidAusbeute 59 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

4-Iodo-2-methylaniline (233 mg, 1.00 mmol) and 3-fluoropyridine-4-carboxylic acid (141 mg, 1.00 mmol) were dissolved in dry THF (6.0 ml) under argon and the mixture was cooled to −78° C. A solution of LiHMDS (1.0M in THF, 3.5 ml) was added and the reaction mixture was allowed to warm to ambient temperature. After 36 h the reaction was quenched by adding solid NH4Cl. After filtration the volatiles were removed in vacuo and the crude material was purified by flash chromatography using silica gel and a gradient of 0-10% methanol in DCM as eluent to give 208 mg (588 μmol; 59% yield) of pure desired product.

Aufarbeitung

  1. temperatureto warm to ambient temperature
  2. customAfter 36 h the reaction was quenched
  3. additionby adding solid NH4Cl
  4. filtrationAfter filtration the volatiles
  5. customwere removed in vacuo
  6. customthe crude material was purified by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-33b761c65db04d79ba5693157d6cd85b
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08524911B2

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