Diisopropylethylamine → N-(3-Fluoro-4-(5-methyl-6-(2-(4-methylpiperazin-1-yl)ethoxy)pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

HRID 1393941ノート

反応式

HRID 1393941 の反応式
[F:1][C:2]1[CH:3]=[C:4]([NH2:29])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:14]2=[C:15]([CH3:28])[C:16]([O:18][CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]3)=[CH:17][N:13]2[N:12]=[CH:11][N:10]=1.[F:30][C:31]1[CH:36]=[CH:35][C:34]([N:37]2[CH:42]=[CH:41][CH:40]=[C:39]([C:43](O)=[O:44])[C:38]2=[O:46])=[CH:33][CH:32]=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>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([NH:29][C:43]([C:39]2[C:38](=[O:46])[N:37]([C:34]3[CH:33]=[CH:32][C:31]([F:30])=[CH:36][CH:35]=3)[CH:42]=[CH:41][CH:40]=2)=[O:44])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:14]2=[C:15]([CH3:28])[C:16]([O:18][CH2:19][CH2:20][N:21]3[CH2:22][CH2:23][N:24]([CH3:27])[CH2:25][CH2:26]3)=[CH:17][N:13]2[N:12]=[CH:11][N:10]=1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210815271-(4-Fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acidHCID 210816093-Fluoro-4-(5-methyl-6-(2-(4-methylpiperazin-1-yl)ethoxy)pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)benzenamine

生成物 1

HCID 16112844N-(3-Fluoro-4-(5-methyl-6-(2-(4-methylpiperazin-1-yl)ethoxy)pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide収率 64%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 3-fluoro-4-(5-methyl-6-(2-(4-methylpiperazin-1-yl)ethoxy)pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)benzenamine 30 mg, 0.075 mmol) and 1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid in DMF (1.0 mL) at room temperature were added HATU (57 mg, 0.15 mmol, Perseptive Biosystem), and DIEA (0.05 mL, 0.3 mmol, Aldrich). The reaction mixture was stirred at rt for 1 h, and was then quenched by the addition of 2 mL of methanol. The reaction mixture was purified by preparative HPLC. The desired fractions were combined, concentrated in vacuo, and neutralized to pH 8 with aq. K2HPO4. The title compound (30 mg, 64%) was obtained as a white solid which was collected by filtration and dried under vaccum. 1H NMR (DMSO-d6) δ 12.09 (br s, 1H), 8.58 (dd, 1H, J=7.15, 2.20 Hz, 1H), 8.12 (dd, 1H, J=6.60, 1.65 Hz), 7.98 (s, 1H), 7.95 (d, 2H, J=3.85 Hz), 7.62-7.59 (m, 2H), 7.45-7.40 (m, 4H), 6.72 (t, 1H, J=9.90 Hz), 4.13 (t, 2H, J=5.5 Hz), 2.71 (d, 2H, J=5.5 Hz), 2.60-2.25 (m, 8H), 2.35 (s, 3H), 2.16 (s, 3H); MS(ESI30) m/z 616.40 (M+H)+.

後処理

  1. customwas then quenched by the addition of 2 mL of methanol
  2. customThe reaction mixture was purified by preparative HPLC
  3. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-2d1803b4d90645b4adb90d6a46b1f1c7
出典データセット
uspto-grants-2008_03
特許番号
US07348325B2

反応ノート

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