Potassium Carbonate → Cinacalcet Impurity 8

HRID 871114

反応式

HRID 871114 の反応式
[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

参加物

5

反応物 3

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

生成物 1

HCID 86660714Cinacalcet Impurity 8

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
27.5 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-01db2531b03245d887530eefbd14bc25
出典データセット
uspto-grants-2015_03
特許番号
US08969623B2

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