Potassium Carbonate → Cinacalcet Impurity 8

HRID 871114

Reaktionsgleichung

Reaktionsgleichung von HRID 871114
[CH3:1][C@@H:2]([NH:13][CH2:14][CH2:15][CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:22]=1)[C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=12.Cl.C(=O)([O-])[O-].[K+].[K+].Br[CH2:35][CH2:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([C:44]([F:47])([F:46])[F:45])[CH:39]=1>C1(C)C=CC=CC=1>[C:3]1([CH:2]([N:13]([CH2:35][CH2:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([C:44]([F:45])([F:46])[F:47])[CH:39]=2)[CH2:14][CH2:15][CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[C:21]([C:23]([F:24])([F:25])[F:26])[CH:22]=2)[CH3:1])[C:8]2[C:7](=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=1

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 156418Cinacalcet HydrochlorideHCID 197833671-(3-Bromopropyl)-3-(trifluoromethyl)benzene

Produkt 1

HCID 86660714Cinacalcet Impurity 8

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
27.5 °C

Versuchsvorschrift

To a stirred solution of Cinacalcet hydrochloride (1, 10 g, 0.028 mol) in toluene (150 mL) was added potassium carbonate (7.74 g, 0.056 mol) followed by 1-(3-bromopropyl)-3-(trifluoromethyl)benzene (5, 14.95 g, 0.056 mol) under stirring at 25-30° C. The reaction mass was heated and stirred at 110-111° C. for 48 h. Upon completion of the reaction (by TLC), the reaction mass was cooled and quenched with water (100 mL). The organic layer was separated, washed with water (100 mL), and concentrated under reduced pressure to obtain a thick oil. The crude oil was then purified by column chromatography on silica gel (70 mm×60 cm column) by eluting with chloroform to afford the title compound as a thick transparent oil. Yield: 10.50 g (69.03%); HPLC purity: 91.22%; IR (NaCl) cm−1: 3441, 3049, 2940, 2861, 1596, 1492, 1449, 1331, 900, 702, 661; MS: m/z=544.0 [M+H]+; 1H NMR (400 MHz, CDCl3): δ=1.35-1.37 (d, 3H), 1.57-1.63 (m, 4H), 2.42-2.46 (t, 4H), 2.52-2.55 (t, 4H), 4.60-4.62 (m, 1H), 7.23-7.25 (d, J=8.0 Hz, 1H), 7.32 (s, 2H), 7.37-7.41 (t, 3H), 7.47-7.51 (m, 6H), 7.76-7.78 (d, J=8.0 Hz, 1H), 7.87-7.89 (dd, 1H), 8.42-8.44 (d, J=8.0 Hz, 1H). 13C NMR (100 MHz, DMSO-d6): δ=15.46 (CH3), 29.38 (CH2), 32.99 (CH2), 50.03 (CH2), 56.90 (CH), 122.68, 122.72, 122.76, 123.37, 124.78, 124.83, 124.86, 124.91, 125.58, 125.68, 125.72 (CF3), 128.88, 129.28, 129.33, 129.40, 129.49, 129.58, 129.60, 129.91, 132.06, 132.63, 134.04, 140.62, 144.01.

Aufarbeitung

  1. temperatureThe reaction mass was heated
  2. stirringstirred at 110-111° C. for 48 h
  3. customUpon completion of the reaction (by TLC)
  4. temperaturethe reaction mass was cooled
  5. customquenched with water (100 mL)
  6. customThe organic layer was separated
  7. washwashed with water (100 mL)
  8. concentrationconcentrated under reduced pressure
  9. customto obtain a thick oil
  10. customThe crude oil was then purified by column chromatography on silica gel (70 mm×60 cm column)
  11. washby eluting with chloroform

Quellen und Nachweise

ORD-Eintrag
ord-01db2531b03245d887530eefbd14bc25
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08969623B2

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