Tris(hydroxymethyl)aminomethane → N-(3-{3-[2-(1,2,3,4-tetrahydro-7-isoquinolinylamino)-4-pyrimidinyl]-pyrazolo[1,5-a]pyridin-2-yl}phenyl)benzamide

HRID 1159899ノート

反応式

HRID 1159899 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24]4[CH:29]=[CH:28][CH:27]=[C:26](F)[CH:25]=4)[N:18]=3)=[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.N1[CH:36]=[CH:35][CH:34]=[C:33]([C:37](Cl)=[O:38])[CH:32]=1.[CH2:40](O)C(N)(CO)CO.[CH2:48]([N:50](CC)[CH2:51]C)[CH3:49]>C1COCC1>[CH2:51]1[C:26]2[C:27](=[CH:28][CH:29]=[C:24]([NH:23][C:19]3[N:18]=[C:17]([C:16]4[C:8]([C:4]5[CH:3]=[C:2]([NH:1][C:37](=[O:38])[C:33]6[CH:34]=[CH:35][CH:36]=[CH:40][CH:32]=6)[CH:7]=[CH:6][CH:5]=5)=[N:9][N:10]5[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=45)[CH:22]=[CH:21][N:20]=3)[CH:25]=2)[CH2:49][CH2:48][NH:50]1

参加物

6

反応物 4

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 8471TriethylamineHCID 82604Nicotinoyl chlorideHCID 595114034-[2-(3-aminophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-(3-fluorophenyl)-2-pyrimidinamine

生成物 1

HCID 59513880N-(3-{3-[2-(1,2,3,4-tetrahydro-7-isoquinolinylamino)-4-pyrimidinyl]-pyrazolo[1,5-a]pyridin-2-yl}phenyl)benzamide

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 100 mg (0.25 mmol) of 4-[2-(3-aminophenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-(3-fluorophenyl)-2-pyrimidinamine in THF at rt was added 63 mg (0.353 mmol) of 3-pyridinecarbonyl chloride. The reaction mixture was allowed to stir for 30 min. At this time, 3.0 eq of PS-Trisamine resin was added and the resulting slurry was allowed to stir overnight. Excess triethylamine was added and the resin was removed by filtration. The reaction mixture was concentrated to dryness and the product was triturated from DCM to give 20 mg of the title compound as a yellow solid: 1H-NMR (d6-DMSO, 400 MHz) δ 6.59 (d, 1H, J=5.5 Hz), 6.73 (td, 1H, J=7.9 and 2.5 Hz), 7.14 (td, 1H, J=7.0 and 1.5 Hz), 7.26 (dd, 1H, J=15.2 and 6.9 Hz), 7.35 (d, 1H, J=7.6 Hz), 7.45-7.58 (m, 4H), 7.80 (d, 1H, J=12.0 Hz), 7.95 (d, 1H, J=8.2 Hz), 8.10 (s, 1H), 8.29 (d, 1H, J=8.6 Hz), 8.32 (d, 1H, J=5.4 Hz), 8.50 (d, 1H, J=8.6 Hz), 8.76 (dd, 1H, J=4.7 and 1.5 Hz), 8.86 (d, 1H, J=7.1 Hz), 9.10 (s, 1H), 9.81 (s, 1H), and 10.57 (s, 1H); HRMS calcd for C29H20FN7O: 501.1713, found: 502.1801 (M+H+).

後処理

  1. stirringto stir overnight
  2. customthe resin was removed by filtration
  3. concentrationThe reaction mixture was concentrated to dryness
  4. customthe product was triturated from DCM

出典と根拠

ORDレコード
ord-784a4f88b9c445a2916fda4dc287cbe0
出典データセット
uspto-grants-2010_10
特許番号
US07812022B2

反応ノート

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