Triethylamine → (2R)-N-[(2R)-2-hydroxy-2-(3-pyridinyl)ethyl]-6-iodo-3,4-dihydro-2H-chromene-2-carboxamide

HRID 896864Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 896864
Cl.Cl.[NH2:3][CH2:4][C@@H:5]([C:7]1[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=1)[OH:6].ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.[I:30][C:31]1[CH:32]=[C:33]2[C:38](=[CH:39][CH:40]=1)[O:37][C@@H:36]([C:41](O)=[O:42])[CH2:35][CH2:34]2>ClCCl>[OH:6][C@H:5]([C:7]1[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=1)[CH2:4][NH:3][C:41]([C@H:36]1[CH2:35][CH2:34][C:33]2[C:38](=[CH:39][CH:40]=[C:31]([I:30])[CH:32]=2)[O:37]1)=[O:42]

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 9966213(2R)-6-Iodochromane-2-carboxylic acidHCID 69103521(1R)-2-amino-1-(3-pyridyl)ethanol dihydrochloride

Produkt 1

HCID 59118145(2R)-N-[(2R)-2-hydroxy-2-(3-pyridinyl)ethyl]-6-iodo-3,4-dihydro-2H-chromene-2-carboxamideAusbeute 74 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

(1R)-2-Amino-1-(3-pyridinyl)ethanol dihydrochloride (U.S. Pat. No. 6,051,586) (5.73 g, 27.1 mmol), 1-hydroxybenzotriazole (6.67 g, 49.3 mmol), 1-(3-dimethylaminopropyl)-3-ethylcabodiimide hydrochloride (9.46 g, 49.3 mmol), and triethylamine (13.8 mL, 9.98 g, 98.7 mmol) were added successively to a stirred solution of (2R)-6-iodo-3,4-dihydro-2H-chromene-2-carboxylic acid (Example 7, Method A, 7.50 g, 24.7 mmol) in dichloromethane (100 mL). The reaction was stirred for 18 hours and then diluted with dichloromethane (300 mL). The solution was washed with saturated aqueous sodium bicarbonate (300 mL) and then the aqueous layer was back-extracted with dichloromethane (2×100 mL). The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography of the residue over silica gel using 5-10% methanol/ethyl acetate gave the product (7.80 g, 74%) as a white solid: 1H NMR (acetone-d6, δ): 8.55 (d, J=1.6 Hz, 1 H), 8.44 (dd, J=4.7, 1.6 Hz, 1 H), 7.71 (ddd, J=7.9, 1.8, 1.8 Hz, 1 H), 7.59 (s, 1 H), 7.35-7.42 (m, 2 H), 7.27 (dd, J=7.9, 4.7 Hz, 1 H), 6.63 (d, 9.6 Hz, 1 H), 4.98 (d, J=4.2 Hz, 1 H), 4.85-4.93 (m, 1 H), 4.53 (dd, J=8.8, 3.4 Hz, 1 H), 3.38-3.70 (m, 2 H), 2.61-2.91 (m, 4 H), 2.16-2.28 (m, 2 H), 1.85-1.99 (m, 1 H); mass spectroscopy gave m/z=425.1 [M+H]+.

Aufarbeitung

  1. washThe solution was washed with saturated aqueous sodium bicarbonate (300 mL)
  2. extractionthe aqueous layer was back-extracted with dichloromethane (2×100 mL)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-2aca2dedbcee4bcf966a5280dca8b0ed
Quelldatensatz
uspto-grants-2005_07
Patentnummer
US06919371B2

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