1-(7-Amino-3,4-dihydroisoquinolin-2(1H)-YL)-2,2,2-trifluoroethanone → Trifluoroacetamide pyrazolopyridazine

HRID 1159897ノート

反応式

HRID 1159897 の反応式
ClC1N=C(C2C(C3C=C(NC(=O)C4C(F)=CC=CC=4F)C=CC=3)=[N:10][N:11]3C=CC=CC=23)C=CN=1.[F:34][C:35]([F:50])([F:49])[C:36]([N:38]1CCC2[C:40](=[CH:41][C:42]([NH2:48])=[CH:43]C=2)[CH2:39]1)=[O:37]>CC(O)C>[NH:10]1[C:41]2[CH:40]=[CH:39][N:38]=[N:48][C:42]=2[CH:43]=[N:11]1.[F:34][C:35]([F:50])([F:49])[C:36]([NH2:38])=[O:37]

参加物

4

反応物 2

HCID 107527801-(7-Amino-3,4-dihydroisoquinolin-2(1H)-YL)-2,2,2-trifluoroethanoneHCID 59513803N-{3-[3-(2-Chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluorobenzamide

生成物 1

HCID 86618777Trifluoroacetamide pyrazolopyridazine収率 349.1%

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

反応条件

温度
160 °C

実験手順

A mixture of N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluorobenzamide (200 mg, 0.43 mmol) and 2-(trifluoroacetyl)-1,2,3,4-tetrahydro-7-isoquinolinamine (211 mg, 0.86 mmol) in a few mL i-PrOH was heated in a microwave apparatus at 160° C. until the reaction was complete. The by partitioning the reaction mixture between saturated aqueous NaHCO3 and CHCl3. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated to give a residue that was purified by silica gel chromatography to afford the intermediate trifluoroacetamide pyrazolopyridazine (350 mg). A portion of this material (250 mg) was subjected to similar conditions as described in Example 62, step F to afford the title compound (198 mg) as a tan powder. LC-MS (AP)+=574.07. 1H NMR (400 MHz, DMSO-d6) δ 2.59 (t, 2H, J=5.5), 2.89 (t, 2H, J=5.5), 3.74 (s, 2H), 6.46 (d, 1H, J=5.1), 6.90 (d, 1H, J=8.2), 7.10 (t, 1H, J=6.7), 7.22 (d, 1H, J=8.0), 7.24 (d, 1H, J=7.9), 7.32 (s, 1H, 7.34 (s, 1H), 7.44-7.48 (m, 3H), 7.53-7.60 (m, 1H), 7.80 (d, 1H, J=8.0), 7.97 (s, 1H), 8.21 (d, 1H, J=5.3), 8.46 (d, 1H, J=9.1), 8.82 (d, 1H, J=6.7), 9.37 (s, 1H).

後処理

  1. customThe by partitioning the reaction mixture between saturated aqueous NaHCO3 and CHCl3
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a residue that
  7. customwas purified by silica gel chromatography

出典と根拠

ORDレコード
ord-623f42e7bad04e7b8c8a46cd85a44a54
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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