Sodium Bicarbonate → 6-{5-[(cyclopropylamino)carbonyl]-3-fluoro-2-methylphenyl}-N-(1,1-dimethylethyl)-3-pyridinecarboxamide

HRID 1174617Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1174617
[C:1]([NH:5][C:6](=[O:14])[C:7]1[CH:12]=[CH:11][C:10](Cl)=[N:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].[CH:15]1([NH:18][C:19]([C:21]2[CH:22]=[C:23]([F:31])[C:24]([CH3:30])=[C:25](B(O)O)[CH:26]=2)=[O:20])[CH2:17][CH2:16]1.C(=O)([O-])O.[Na+]>CC(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:15]1([NH:18][C:19]([C:21]2[CH:22]=[C:23]([F:31])[C:24]([CH3:30])=[C:25]([C:10]3[N:9]=[CH:8][C:7]([C:6]([NH:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:14])=[CH:12][CH:11]=3)[CH:26]=2)=[O:20])[CH2:17][CH2:16]1

Komponenten

6

Edukt 3

HCID 516892Sodium BicarbonateHCID 11816697N-tert-butyl-6-chloronicotinamideHCID 21914527(5-(Cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl)boronic acid2×

Produkt 1

HCID 686803146-{5-[(cyclopropylamino)carbonyl]-3-fluoro-2-methylphenyl}-N-(1,1-dimethylethyl)-3-pyridinecarboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 3776IsopropanolLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

N-tertbutyl-6-Chloronicotinamide (100 mg), {5-[(cyclopropylamino)carbonyl]-3-fluoro-2-methylphenyl}boronic acid (Intermediate 6, 100 mg), tetrakis(triphenylphosphine)palladium (10 mg) and aqueous sodium hydrogen carbonate (4 ml) were mixed in propan-2-ol (8 ml) and heated at 90° C. under nitrogen for 18 hrs. The solvents were evaporated from the cooled reaction under vacuum and the residue dissolved as far as possible in ethylacetate. The solution was applied to an SPE (SCX, 10 g) and washed with ethyl acetate. The product was eluted from the column with methanol/0.880 ammonia, and the solvents evaporated in vacuo. The residue was redissolved in ethyl acetate and filtered through an SPE (silica, 0.5 g). The filtrate was reduced to dryness under vacuum and triturated with ether to give 6-{5-[(cyclopropylamino)carbonyl]-3-fluoro-2-methylphenyl}-N-(1,1-dimethylethyl)-3-pyridinecarboxamide.

Aufarbeitung

  1. customThe solvents were evaporated from the cooled reaction under vacuum
  2. dissolutionthe residue dissolved as far as possible in ethylacetate
  3. washwashed with ethyl acetate
  4. washThe product was eluted from the column with methanol/0.880 ammonia
  5. customthe solvents evaporated in vacuo
  6. dissolutionThe residue was redissolved in ethyl acetate
  7. filtrationfiltered through an SPE (silica, 0.5 g)
  8. customtriturated with ether

Quellen und Nachweise

ORD-Eintrag
ord-35ac930c931a481c97b3a1ff567fa6c1
Quelldatensatz
uspto-grants-2010_11
Patentnummer
US07838540B2

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