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 1755316Notes

Reaction equation

HRID 1755316 reaction equation
[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

Participants

7

Reactant 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

Product 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)benzamideYield 24%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-ba4bddf74edb44db86df8838e8064f8a
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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