5-Bromopyridine-2,3-diamine → HCID 178519518、化合物

HRID 499179

反応式

HRID 499179 の反応式
[Br:1][C:2]1[CH:3]=[C:4]([NH2:9])[C:5]([NH2:8])=[N:6][CH:7]=1.[F:10][C:11]([F:36])([F:35])[C:12]1[CH:34]=[CH:33][CH:32]=[CH:31][C:13]=1[C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:22]2[N:27]=[N:26][C:25]([C:28](O)=O)=[CH:24][CH:23]=2)[CH2:18][CH2:17]1)=[O:15]>O=P(Cl)(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[N:9]=[C:28]([C:25]3[N:26]=[N:27][C:22]([N:19]4[CH2:18][CH2:17][N:16]([C:14]([C:13]5[CH:31]=[CH:32][CH:33]=[CH:34][C:12]=5[C:11]([F:36])([F:10])[F:35])=[O:15])[CH2:21][CH2:20]4)=[CH:23][CH:24]=3)[NH:8][C:5]2=[N:6][CH:7]=1

参加物

4

反応物 2

HCID 6911565-Bromopyridine-2,3-diamineHCID 454873706-[4-(2-TRIFLUOROMETHYLBENZOYL)PIPERAZIN-1-YL]PYRIDAZINE-3-CARBOXYLIC Acid

生成物 1

HCID 178519518HCID 178519518、化合物収率 74%

試薬・触媒・溶媒 1

HCID 24813Phosphorus oxychloride溶媒

反応条件

温度
12.5 °C

実験手順

A mixture of 5-bromopyridine-2,3-diamine (0.188 g, 1.000 mmol) and 6-[4-(2-trifluoromethylbenzoyl)piperazin-1-yl]pyridazine-3-carboxylic acid (0.380 g, 1.000 mmol) in POCl3 (7 mL) was heated to reflux for 24 hours. The solvent was evaporated in vacuo, and the dark residue was neutralized with ice-cold NaOH solution. The mixture was extracted with ethyl acetate. The organic layer was separated, dried over MgSO4 and filtered through the short pad of silica gel. The filtrate was concentrated, ether was added. After cooling to 10-15° C. the white precipitation started to form. This was filtered off and dried in vacuo to yield {4-[6-(6-bromo-3H-imidazo[4,5-b]pyridin-2-yl)pyridazin-3-yl]piperazin-1-yl}-(2-trifluoromethylphenyl)methanone in 74% yield (0.394 g, 0.810 mmol). 1H NMR (300 MHz, CDCl3) δ 13.64 (br., s, 1H), 8.40 (s, 1H), 8.17 (d, J=9.6 Hz, 1H), 8.03 (br, s, 1H), 7.82 (d, J=7.8 Hz, 1H), 7.76 (t, J=7.4 Hz, 1H), 7.65 (t, J=7.5 Hz, 1H), 7.43 (d, J=9.6 Hz, 1H), 3.90-3.20 (m, 8H13C NMR (75 MHz, CDCl3) δ 166.8, 159.9, 152.8, 144.9, 143.5, 135.0, 133.4, 130.1, 128.0, 127.1, 127.0, 126.9, 126.0, 125.9, 125.6, 122.4, 113.8, 46.4, 44.5, 44.3, 41.2. MS (ES+) m/z 532, 534 (M+1).

後処理

  1. temperaturewas heated
  2. temperatureto reflux for 24 hours
  3. customThe solvent was evaporated in vacuo
  4. extractionThe mixture was extracted with ethyl acetate
  5. customThe organic layer was separated
  6. dry with materialdried over MgSO4
  7. filtrationfiltered through the short pad of silica gel
  8. concentrationThe filtrate was concentrated
  9. additionether was added
  10. customthe white precipitation
  11. customto form
  12. filtrationThis was filtered off
  13. customdried in vacuo

出典と根拠

ORDレコード
ord-2ba4e1346fb04317bf9b9a43d7afcdab
出典データセット
uspto-grants-2010_08
特許番号
US07767677B2

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