1-Methylimidazole → 4-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)-N-(2-(pyridin-4-yl)ethyl)benzamide

HRID 1755316Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1755316
[CH3:1][CH:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[N:12]=[C:11]([NH:13][C:14]2[C:15]3[N:16]([CH:29]=[CH:30][N:31]=3)[N:17]=[C:18]([C:20]3[CH:28]=[CH:27][C:23]([C:24]([OH:26])=O)=[CH:22][CH:21]=3)[CH:19]=2)[CH:10]=[CH:9][CH:8]=1.[N:32]1[CH:37]=[CH:36][C:35]([CH2:38][CH2:39][NH2:40])=[CH:34][CH:33]=1.CCN=C=NCCCN(C)C.CN1C=CN=C1>CN(C=O)C.ClCCl>[CH3:1][CH:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[N:12]=[C:11]([NH:13][C:14]2[C:15]3[N:16]([CH:29]=[CH:30][N:31]=3)[N:17]=[C:18]([C:20]3[CH:21]=[CH:22][C:23]([C:24]([NH:40][CH2:39][CH2:38][C:35]4[CH:36]=[CH:37][N:32]=[CH:33][CH:34]=4)=[O:26])=[CH:27][CH:28]=3)[CH:19]=2)[CH:10]=[CH:9][CH:8]=1

Komponenten

7

Edukt 4

HCID 13901-MethylimidazoleHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 832754-PyridineethanamineHCID 715256154-(8-(6-(2-Methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid

Produkt 1

HCID 715256164-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)-N-(2-(pyridin-4-yl)ethyl)benzamideAusbeute 24 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A mixture of 4-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (41 mg, 0.1 mmol), 2-(pyridin-4-yl)ethanamine (15 mg, 0.12 mmol), EDCI (77 mg, 0.4 mmol), N-methyl-imidazole (33 mg, 0.4 mmol), dichloromethane (3 mL) and DMF (0.5 mL) was stirred at room temperature for 16 h. The solution was concentrated in vacuo, triturated with water (10 mL×3), and the residue purified by chromatography (silica gel, 200-300 mesh, CH2Cl2:MeOH=30:1) to give 4-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)-N-(2-(pyridin-4-yl)ethyl)benzamide (12 mg, 24%) as a yellow oil. 1H NMR (300 MHz, DMSO): δ 9.68 (s, 1H), 8.81 (s, 1H), 8.74-8.70 (m, 1H), 8.49-8.47 (m, 2H), 8.23 (s, 1H), 8.03-7.95 (m, 4 h), 7.68 (s, 1H), 7.46 (t, 1H, J=8.4 Hz), 7.30 (s, 1H), 7.29 (s, 1H), 6.75 (d, 1H, J=7.5 Hz), 6.09 (d, 1H, J=8.1 Hz), 4.25-4.21 (m, 1H), 3.61-3.56 (m, 2H), 3.47-3.40 (m, 2H), 2.92 (t, 2H, J=6.6 Hz), 2.11-1.99 (m, 3H), 1.71 (s, 1H), 0.85 (d, 3H, J=6.6 Hz). LC-MS: [M+H]+, 519, tR=1.333 min, HPLC: 100% at 214 nm, 100% at 254 nm, tR=5.008 min.

Aufarbeitung

  1. concentrationThe solution was concentrated in vacuo
  2. customtriturated with water (10 mL×3)
  3. customthe residue purified by chromatography (silica gel, 200-300 mesh, CH2Cl2:MeOH=30:1)

Quellen und Nachweise

ORD-Eintrag
ord-ba4bddf74edb44db86df8838e8064f8a
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09169259B2

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