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Sodium Carbonate → 6-[5-(Cyclopropylcarbamoyl)-2-Methylphenyl]-N-(Cyclopropylmethyl)pyridine-3-Carboxamide

HRID 2037254
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2037254
Cl[C:2]1[CH:14]=[CH:13][C:5]([C:6]([NH:8][CH2:9][CH:10]2[CH2:12][CH2:11]2)=[O:7])=[CH:4][N:3]=1.[CH:15]1([NH:18][C:19](=[O:36])[C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[C:22](B3OC(C)(C)C(C)(C)O3)[CH:21]=2)[CH2:17][CH2:16]1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=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:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[C:22]([C:2]3[CH:14]=[CH:13][C:5]([C:6]([NH:8][CH2:9][CH:10]4[CH2:12][CH2:11]4)=[O:7])=[CH:4][N:3]=3)[CH:21]=2)=[O:36])[CH2:16][CH2:17]1
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 112758456-chloro-N-(cyclopropylmethyl)pyridine-3-carboxamide2×HCID 21914577N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide2×

Produkt 1

HCID 219145196-[5-(Cyclopropylcarbamoyl)-2-Methylphenyl]-N-(Cyclopropylmethyl)pyridine-3-Carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397
HCID 178418397, Verbindung
Katalysator
HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

6-Chloro-N-cyclopropylmethylnicotinamide (Intermediate 1) (25.5 mg, 0.10 mmol) and N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide (Intermediate 8) (30 mg, 0.10 mmol), aqueous sodium carbonate (2N, 0.5 ml) and tetrakis(triphenylphosphine)palladium (4 mg) were heated at 90° C. in DMF (1 ml) for 3 hours. The reaction was absorbed onto silica, applied to a bond-elut (5 g, silica) and eluted with an ethylacetate/cyclohexane (0 to 100%) and then acetone. The solvent was evaporated from the product fractions under vacuum and the residue triturated with ether to 6-(5-cyclopropylcarbamoyl-2-methyl-phenyl)-N-cyclopropylmethyl-nicotinamide as a cream solid. LCMS: retention time 2.70 min, MH+ 350. NMR: δH [2H6]-DMSO 9.11, (1H, s), 8.84, (1H, t), 8.48, (1H, d), 8.31, (1H, dd), 7.88, (1H, s), 7.81, (1H, d), 7.70, (1H, d), 7.41, (1H, d), 3.20, (1H, t), 2.86, (1H, m), 2.37, (3H, s), 1.06, (1H, m), 0.69, (2H, m), 0.57, (2H, m), 0.46, (2H, m), 0.26, (2H, m).

Aufarbeitung

  1. customThe reaction was absorbed onto silica
  2. washeluted with an ethylacetate/cyclohexane (0 to 100%)
  3. customThe solvent was evaporated from the product fractions under vacuum
  4. customthe residue triturated with ether to 6-(5-cyclopropylcarbamoyl-2-methyl-phenyl)-N-cyclopropylmethyl-nicotinamide as a cream solid

Quellen und Nachweise

ORD-Eintrag
ord-c93a38a725df4f169c8d50afbaefe464
Quelldatensatz
uspto-grants-2013_11
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08575204B2

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