4-(Methylcarbamoyl)benzeneboronic acid → 4-(2-{2-Methoxy-4-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-phenylamino}-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-N-methyl-benzamide

HRID 1261965ノート

反応式

HRID 1261965 の反応式
Br[C:2]1[N:10]2[C:5]([CH:6]=[N:7][C:8]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([N:18]4[CH2:23][CH2:22][CH:21]([N:24]5[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]5)[CH2:20][CH2:19]4)=[CH:14][C:13]=3[O:31][CH3:32])=[N:9]2)=[CH:4][CH:3]=1.[CH3:33][NH:34][C:35]([C:37]1[CH:42]=[CH:41][C:40](B(O)O)=[CH:39][CH:38]=1)=[O:36]>>[CH3:32][O:31][C:13]1[CH:14]=[C:15]([N:18]2[CH2:23][CH2:22][CH:21]([N:24]3[CH2:25][CH2:26][N:27]([CH3:30])[CH2:28][CH2:29]3)[CH2:20][CH2:19]2)[CH:16]=[CH:17][C:12]=1[NH:11][C:8]1[N:7]=[CH:6][C:5]2=[CH:4][CH:3]=[C:2]([C:40]3[CH:41]=[CH:42][C:37]([C:35]([NH:34][CH3:33])=[O:36])=[CH:38][CH:39]=3)[N:10]2[N:9]=1

参加物

3

反応物 2

HCID 27735264-(Methylcarbamoyl)benzeneboronic acidHCID 66711255(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-{2-methoxy-4-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-phenyl}-amine

生成物 1

HCID 667115164-(2-{2-Methoxy-4-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-phenylamino}-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-N-methyl-benzamide収率 54.1%

実験手順

Following a procedure similar to Example 241, (7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-{2-methoxy-4-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-phenyl}-amine (0.10 g, 0.00020 mol) and 4-(N-Methylaminocarbonyl)phenylboronic acid (0.039 g, 0.00022 mol). Purification by Isco chromatography gave 4-(2-{2-Methoxy-4-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-phenylamino}-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-N-methyl-benzamide as a tan solid (0.06 g, 50%). MP 112-114° C.; LCMS (m/e) 555 (M+1); 1H-NMR (DMSO, 400 MHz) δ 8.94 (s, 1H), 8.28 (d, 1H, J=8.53 Hz), 7.90 (d, 1H, J=8.52 Hz), 7.85 (s, 1H), 7.71 (d, 1H, J=8.68 Hz), 7.28 (d, 1H, J=4.80 Hz), 6.94 (d, 1H, J=4.80 Hz), 6.69 (d, 1H, J=2.40 Hz), 3.83 (s, 3H), 3.74 (d, 1H, J=2.00 Hz), 2.82 (d, 2H, J=4.52 Hz), 2.68 (m, 3H), 2.33 (m, 4H), 2.15 (s, 3H), 1.90-1.75 (m, 2H), 1.60-1.48 (m, 2H), 1.25 (s, 1H), 1.18 (br s, 2H).

後処理

  1. customPurification by Isco chromatography

出典と根拠

ORDレコード
ord-1ae459c9343241229c572b15d9b9e166
出典データセット
uspto-grants-2013_06
特許番号
US08471005B2

反応ノート

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