Sodium Carbonate → 2-Amino-5-[2-(3,4-dimethoxy-phenyl)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-nicotinonitrile

HRID 2409554Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2409554
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[S:15][C:14]3=[N:16][CH:17]=[C:18](I)[N:13]3[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[NH2:20][C:21]1[N:28]=[CH:27][C:26](B2OC(C)(C)C(C)(C)O2)=[CH:25][C:22]=1[C:23]#[N:24].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[NH2:20][C:21]1[N:28]=[CH:27][C:26]([C:18]2[N:13]3[C:14]([S:15][C:11]([C:5]4[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=4)=[N:12]3)=[N:16][CH:17]=2)=[CH:25][C:22]=1[C:23]#[N:24]

Komponenten

5

Edukt 3

HCID 10340Sodium CarbonateHCID 667169462-(3,4-Dimethoxy-phenyl)-5-iodo-imidazo[2,1-b][1,3,4]thiadiazoleHCID 672836162-Amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinonitrile

Produkt 1

HCID 469411282-Amino-5-[2-(3,4-dimethoxy-phenyl)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-nicotinonitrileAusbeute 22 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A mixture of 2-(3,4-dimethoxy-phenyl)-5-iodo-imidazo[2,1-b][1,3,4]thiadiazole (0.1 g, 0.258 mmol, 1 eq), 2-amino-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-nicotinonitrile (0.11 g, 0.449 mmol, 1.74 eq), PdCl2(Ph3P)2 (36 mg, 0.052 mmol, 0.2 eq) and Na2CO3 (2 M aqueous solution, 0.5 mL) in dioxane was heated at 110° C. for 2.5 h. The reaction was cooled down to it and solvents were removed under reduced pressure. The residue was treated with water, sonicated and then filtered. The solid was washed with water, Et2O, Et2O/MeOH (9:1), and dried. The residue was purified on silica gel (isolute flash Si II, DCM/MeOH 5 to 10% MeOH and biotage, MeOH/DCM, 0% to 10%) to give the desired product (21 mg, 22%). HPLC-MS: (5-100% B in 8 min, 0.8 mL/min, 50° C.): tR=4.68 min, [M+H]+ m/z 379.1; 1H NMR (300 MHz, DMSO) δ 8.91 (d, J=2.4 Hz, 1H), 8.45 (d, J=2.4 Hz, 1H), 7.72 (s, 2H), 7.56 (dd, J=8.4, 2.1 Hz, 1H), 7.48 (d, J=2.1 Hz, 1H), 7.17 (m, 3H), 3.89 (s, 3H), 3.86 (s, 3H).

Aufarbeitung

  1. temperatureThe reaction was cooled down to it and solvents
  2. customwere removed under reduced pressure
  3. additionThe residue was treated with water
  4. customsonicated
  5. filtrationfiltered
  6. washThe solid was washed with water, Et2O, Et2O/MeOH (9:1)
  7. customdried
  8. customThe residue was purified on silica gel (isolute flash Si II, DCM/MeOH 5 to 10% MeOH and biotage, MeOH/DCM, 0% to 10%)

Quellen und Nachweise

ORD-Eintrag
ord-8df65a7d27574fbf87370164da3f6f38
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08815918B2

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