6-chloro-N-(pyridin-4-yl)-8-(pyrimidin-4-ylamino)imidazo[1,2-b]pyridazine-3-carboxamide → HCID 178511636, Verbindung

HRID 1943501Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1943501
Cl[C:2]1[CH:3]=[C:4]([NH:20][C:21]2[CH:26]=[CH:25][N:24]=[CH:23][N:22]=2)[C:5]2[N:6]([C:8]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)=[O:12])=[CH:9][N:10]=2)[N:7]=1.[C@H:27]1([NH2:34])[CH2:32][CH2:31][C@H:30]([NH2:33])[CH2:29][CH2:28]1>CN1C(=O)CCC1.CO>[NH2:33][C@H:30]1[CH2:31][CH2:32][C@H:27]([NH:34][C:2]2[CH:3]=[C:4]([NH:20][C:21]3[CH:26]=[CH:25][N:24]=[CH:23][N:22]=3)[C:5]3[N:6]([C:8]([C:11]([NH:13][C:14]4[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=4)=[O:12])=[CH:9][N:10]=3)[N:7]=2)[CH2:28][CH2:29]1

Komponenten

5

Edukt 2

HCID 596244986-chloro-N-(pyridin-4-yl)-8-(pyrimidin-4-ylamino)imidazo[1,2-b]pyridazine-3-carboxamideHCID 178511674HCID 178511674, Verbindung

Produkt 1

HCID 178511636HCID 178511636, VerbindungAusbeute 14,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A solution of 6-chloro-N-(pyridin-4-yl)-8-(pyrimidin-4-ylamino)imidazo[1,2-b]pyridazine-3-carboxamide (12 mg, 0.033 mmol) in NMP (1 mL) was treated with (trans)-cyclohexane-1,4-diamine (37.4 mg, 0.327 mmol) and heated to 120° C. for 4 hours. The crude reaction product was dissolved in a small amount of MeOH and purified by reversed phase HPLC (YMC ODS-A 5 um 30×250 mm, 10-90% aqueous methanol containing 0.1% TFA, 25 mL/min, 30 min gradient, monitored at 220 nm). The product (retention time=19.202 minutes) was isolated and lyophilized to dryness to afford 6-((trans-4-aminocyclohexyl)amino)-N-4-pyridinyl-8-(4-pyrimidinylamino)imidazo[1,2-b]pyridazine-3-carboxamide (2.1 mg, 8.59%). 1H NMR (500 MHz, DMSO) δ ppm 8.87 (1H, s), 8.65-8.74 (3H, m), 8.51 (1H, d, J=10.45 Hz), 8.25 (2H, d, J=6.60 Hz), 8.21 (2H, s), 7.25 (1H, d, J=6.05 Hz), 3.82-3.93 (1H, m), 3.16-3.24 (1H, m), 2.39 (2H, d, J=14.57 Hz), 2.11-2.22 (3H, m), 1.45-1.68 (4H, m). HPLC Rt=1.888 min (YMC S5 ODS 4.6×50 mm, 10-90% aqueous methanol containing 0.2% H3PO4, 4 min gradient, monitored at 220 nm). [M+H+]=445.0.

Aufarbeitung

  1. customThe crude reaction product
  2. custompurified by reversed phase HPLC (YMC ODS-A 5 um 30×250 mm, 10-90% aqueous methanol containing 0.1% TFA, 25 mL/min, 30 min gradient, monitored at 220 nm)
  3. customThe product (retention time=19.202 minutes) was isolated

Quellen und Nachweise

ORD-Eintrag
ord-b52ddf60d4764226a8c3635e6d111cd0
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08389527B2

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