1-Propanol → 4-(2-Chloro-4-pyrimidinyl)-N-(cyanomethyl)benzamide

HRID 591129Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 591129
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[C:9]([CH2:11][NH:12][C:13]([C:15]1[CH:20]=[CH:19][C:18](B(O)O)=[CH:17][CH:16]=1)=[O:14])#[N:10].C(O)CC.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([C:18]2[CH:19]=[CH:20][C:15]([C:13]([NH:12][CH2:11][C:9]#[N:10])=[O:14])=[CH:16][CH:17]=2)[CH:5]=[CH:4][N:3]=1

Komponenten

6

Edukt 4

HCID 10311-PropanolHCID 775312,4-DichloropyrimidineHCID 516892Sodium BicarbonateHCID 866438164-(Cyanomethyl-carbamoyl)phenyl-boronic acid

Produkt 1

HCID 866438174-(2-Chloro-4-pyrimidinyl)-N-(cyanomethyl)benzamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

To a solution of 2,4-dichloropyrimidine (3.2 g, 0.22 mmol) and 4-(cyanomethylcarbamoyl)phenylboronic acid (3.0 g, 15 mmol) in toluene (146 mL) were added n-propanol (44 mL), aqueous sodium bicarbonate (2M, 22 mL) and tetrakis(triphenylphosphine) palladium[0](850 mg, 0.7 mmol). The reaction was heated at 90° C. for 24 h, then partitioned between ethyl acetate and water. The aqueous layer was extracted twice further with ethyl acetate and the combined organic fractions washed with brine, dried (Na2SO4) filtered and concentrated. Silica gel chromatography using 30-70% ethyl acetate/petroleum spirit as eluent provided 4-(2-chloropyrimidin-4-yl)-N-(cyanomethyl)benzamide as a pale yellow waxy solid (1.35 g, 33%). 1H NMR (300 MHz, d6-DMSO) δ 9.40 (t, J=5.4 Hz, 1H), 8.88 (d, J=5.2 Hz, 1H), 8.32 (d, J=8.7 Hz, 2H), 8.23 (d, J=5.1 Hz, 1H), 8.05 (d, J=8.7 Hz, 2H), 4.36 (d, J=5.4 Hz, 2H); LC-ESI-MS (method B): rt 5.3 min.; m/z 273.2/275.2 [M+H]+.

Aufarbeitung

  1. custompartitioned between ethyl acetate and water
  2. extractionThe aqueous layer was extracted twice further with ethyl acetate
  3. washthe combined organic fractions washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-8a56594d2fad46528469632d43ac6954
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09238628B2

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