Potassium Phosphate, Tribasic → (3-Fluoro-2'-(trifluoromethyl)-[2,4'-bipyridin]-5-yl)methanamine

HRID 711276Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 711276
Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][NH2:9])=[CH:4][C:3]=1[F:10].[F:11][C:12]([F:23])([F:22])[C:13]1[CH:18]=[C:17](B(O)O)[CH:16]=[CH:15][N:14]=1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2].CC(O)CC>[F:10][C:3]1[C:2]([C:17]2[CH:16]=[CH:15][N:14]=[C:13]([C:12]([F:23])([F:22])[F:11])[CH:18]=2)=[N:7][CH:6]=[C:5]([CH2:8][NH2:9])[CH:4]=1

Komponenten

7

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 451588802-(Trifluoromethyl)pyridine-4-boronic acidHCID 53395621(6-Chloro-5-fluoropyridin-3-YL)methanamine

Produkt 1

HCID 67208645(3-Fluoro-2'-(trifluoromethyl)-[2,4'-bipyridin]-5-yl)methanamine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 6568(+-)-2-ButanolLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a flask containing (6-chloro-5-fluoropyridin-3-yl)methanamine 84-1 (353 mg, 2.20 mmol), 2-(trifluoromethyl)pyridin-4-ylboronic acid 33-1 (418 mg, 2.20 mmol), Pd(OAc)2 (29 mg, 0.11 mmol), S-Phos (91 mg, 0.22 mmol) and potassium phosphate (1.40 g, 6.60 mmol) under Argon was added 2-butanol (4 mL). The mixture was stirred at 100° C. for 10 hours. After cooling to room temperature, the mixture was filtered through celite cake. The filtrate was diluted with ethyl acetate, washed with H2O and brine, dried over Na2SO4, and concentrated to dryness by rotary evaporation. The crude product was purified by silica gel flash chromatography, and eluted with 5% methanol containing ˜7N ammonia in dichloromethane to give (3-fluoro-2′-(trifluoromethyl)-2,4′-bipyridin-5-yl)methanamine 84-2 as a pale yellow solid. MS m/z 268.1 (M+1)

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. filtrationthe mixture was filtered through celite cake
  3. additionThe filtrate was diluted with ethyl acetate
  4. washwashed with H2O and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to dryness by rotary evaporation
  7. customThe crude product was purified by silica gel flash chromatography
  8. washeluted with 5% methanol containing ˜7N ammonia in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-24692876f15b4798ab880b7f9b3e0fe1
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09181235B2

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