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 1755316ノート

反応式

HRID 1755316 の反応式
[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

参加物

7

反応物 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

生成物 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)benzamide収率 24%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-ba4bddf74edb44db86df8838e8064f8a
出典データセット
uspto-grants-2015_10
特許番号
US09169259B2

反応ノート

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