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Hydrochloric Acid → HCID 136347347, Verbindung

HRID 601324
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 601324
[NH2:1][CH2:2][C:3]1[C:11]2[S:10](=[O:13])(=[O:12])[N:9]=[C:8]([C:14]3[C:15](=[O:32])[N:16]([CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[C:17]4[C:22]([C:23]=3[OH:24])=[CH:21][CH:20]=[CH:19][CH:18]=4)[NH:7][C:6]=2[S:5][CH:4]=1.C(N(CC)CC)C.N12CCCN=C1CCCCC2.Cl.[C:52](Cl)(=[O:59])[C:53]1[CH:58]=[CH:57][CH:56]=[N:55][CH:54]=1.Cl>O1CCCC1.CN(C)C=O>[CH2:25]([N:16]1[C:17]2[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:23]([OH:24])=[C:14]([C:8]2[NH:7][C:6]3[S:5][CH:4]=[C:3]([CH2:2][NH:1][C:52](=[O:59])[C:53]4[CH:58]=[CH:57][CH:56]=[N:55][CH:54]=4)[C:11]=3[S:10](=[O:13])(=[O:12])[N:9]=2)[C:15]1=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2×HCID 884383-Pyridinecarbonyl chloride, hydrochloride (1:1)4×HCID 136347238HCID 136347238, Verbindung

Produkt 1

HCID 136347347
HCID 136347347, Verbindung
Ausbeute 37,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To the solution of the product of Example 345 (0.015 g, 0.032 mmol) in tetrahydrofuran (0.4 mL) was added triethylamine (0.022 mL, 0.160 mmol), and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.020 mL, 0.129 mmol). The mixture was cooled to 0° C. and nicotinoylchloride hydrochloride (0.007 g, 0.035 mmol) was added. The mixture was stirred for 2.5 hours and then warmed to 23° C. and stirred for 2.5 hours. Additional 1,8 diazabicyclo[5.4.0]undec-7-ene (0.010 mL, 0.068 mmol) and nicotinoylchloride hydrochloride (0.006 g, 0.032 mmol) were added and the mixture was stirred at 23° C. for 15 hours. Added additional nicotinoyl chloride hydrochloride (0.006 g, 0.032 mmol) and stirred at 23° C. for 6 hours. A few drops of N,N-dimethylformamide were added to increase solubility. Added additional nicotinoyl chloride hydrochloride (0.006 g, 0.032 mmol) and stirred at 23° C. for 72 hours. Hydrochloric acid (4 M in dioxane) (0.095 mL, 0.370 mmol) was added and the reaction mixture was concentrated under reduced pressure. The resulting solid was then washed with diethyl ether and water. The solid was dissolved in 1% triethylamine/dichloromethane and purified by preparative thin layer chromatography eluting with 5%(5% triethylamine/methanol)/dichloromethane. The silica gel was washed with 10% (5% triethylamine/methanol)/dichloromethane to give the triethylamine salt of the title compound (0.0068 g, 31%). 1HNMR(500 MHz, DMSO-d6) δ 1.17 (t, J=7.32 Hz, 9 H) 3.09 (q, J=7.32 Hz, 6 H) 4.60 (d, J=4.88 Hz, 2 H) 5.44 (bs, 2 H) 7.00 (bs, 1 H) 7.12 (m, 1 H) 7.26 (m, 5 H) 7.46 (m, 1H) 7.53 (dd, J=7.63, 4.58 Hz, 1 H) 8.12 (d, J=7.32 Hz, 1 H) 8.26 (m, J=7.93 Hz, 1 H) 8.72 (d, J=3.66 Hz, 1 H) 8.86 (bs, 1 H) 9.09 (s, 1 H) 9.16 (bs, 1 H).

Aufarbeitung

  1. temperaturewarmed to 23° C.
  2. stirringstirred for 2.5 hours
  3. stirringthe mixture was stirred at 23° C. for 15 hours
  4. stirringstirred at 23° C. for 6 hours
  5. temperatureto increase solubility
  6. stirringstirred at 23° C. for 72 hours
  7. concentrationthe reaction mixture was concentrated under reduced pressure
  8. washThe resulting solid was then washed with diethyl ether and water
  9. dissolutionThe solid was dissolved in 1% triethylamine/dichloromethane
  10. custompurified by preparative thin layer chromatography
  11. washeluting with 5%(5% triethylamine/methanol)/dichloromethane
  12. washThe silica gel was washed with 10% (5% triethylamine/methanol)/dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-9716b1de07334445bf603150080eeba7
Quelldatensatz
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07902203B2

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