1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)-N-(2-(pyridin-4-yl)ethyl)benzamide

HRID 1755337ノート

反応式

HRID 1755337 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([NH:11][C:12]2[C:13]3[N:14]([CH:27]=[CH:28][N:29]=3)[N:15]=[C:16]([C:18]3[CH:26]=[CH:25][C:21]([C:22]([OH:24])=O)=[CH:20][CH:19]=3)[CH:17]=2)=[N:7][C:8]=1[O:9][CH3:10].[N:30]1[CH:35]=[CH:34][C:33]([CH2:36][CH2:37][NH2:38])=[CH:32][CH:31]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C>CN(C1C=CN=CC=1)C.CN(C=O)C.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([NH:11][C:12]2[C:13]3[N:14]([CH:27]=[CH:28][N:29]=3)[N:15]=[C:16]([C:18]3[CH:19]=[CH:20][C:21]([C:22]([NH:38][CH2:37][CH2:36][C:33]4[CH:34]=[CH:35][N:30]=[CH:31][CH:32]=4)=[O:24])=[CH:25][CH:26]=3)[CH:17]=2)=[N:7][C:8]=1[O:9][CH3:10]

参加物

9

反応物 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 832754-PyridineethanamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 715258044-(8-(5,6-Dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid

生成物 1

HCID 715258054-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)-N-(2-(pyridin-4-yl)ethyl)benzamide収率 72.3%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A mixture of 4-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (47 mg, 0.12 mmol), 2-(pyridin-4-yl)ethanamine (16 mg, 0.132 mmol), HATU (50 mg, 0.132 mmol), DIPEA (18 mg, 0.144 mmol), DMAP (18 mg, 0.144 mmol) and EDCI (28 mg, 0.144 mmol) in DMF (3 mL) was stirred at room temperature for 16 h. Ethyl acetate (50 mL) was added then the mixture was washed with water (2×2 mL) and brine (2×2 mL), then dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was washed with ether and filtered to afford 4-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)-N-(2-(pyridin-4-yl)ethyl)benzamide (43 mg, 72%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 9.96 (s, 1H), 8.71 (t, 1H, J=5.4 Hz), 8.53-8.46 (m, 3H), 8.21 (s, 1H), 8.03-7.94 (m, 4 h), 7.67 (s, 1H), 7.42 (d, 1H, J=8.4 Hz), 7.29-7.27 (m, 2H), 7.11 (d, 1H, J=8.4 Hz), 4.01 (s, 3H), 3.78 (s, 3H), 3.60-3.54 (m, 2H), 2.90 (t, 2H, J=7.2 Hz). LC-MS: [M+H]+, 496, tR=1.226 min, HPLC: 98.86% at 214 nm, 98.46% at 254 nm, tR=3.144 min.

後処理

  1. washthe mixture was washed with water (2×2 mL) and brine (2×2 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated in vacuo
  4. washThe residue was washed with ether
  5. filtrationfiltered

出典と根拠

ORDレコード
ord-772416139bc04472ac7d5530c089a029
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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