Dimethylformamide → 2-(6-Methoxy-[1,5]naphthyridin-4-yl)4,5,6,7-tetrahydro-2H-indazol-5-ylamine

HRID 1176676ノート

反応式

HRID 1176676 の反応式
Br[C:2]1[CH:3]=[CH:4][N:5]=[C:6]2[C:11]=1[N:10]=[C:9]([O:12][CH3:13])[CH:8]=[CH:7]2.COC1[N:17]=[C:18]2[C:23](=[CH:24][CH:25]=1)[N:22]=[CH:21][CH:20]=[C:19]2O.P(Br)(Br)Br.C[N:32](C=O)C>>[CH3:13][O:12][C:9]1[N:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[CH:4][CH:3]=[C:2]2[N:22]1[CH:21]=[C:20]2[C:25]([CH2:24][CH2:23][CH:18]([NH2:17])[CH2:19]2)=[N:32]1

参加物

5

反応物 4

HCID 6228DimethylformamideHCID 24614Phosphorus tribromideHCID 534216178-Bromo-2-methoxy-1,5-naphthyridineHCID 178487891HCID 178487891、化合物

生成物 1

HCID 595606482-(6-Methoxy-[1,5]naphthyridin-4-yl)4,5,6,7-tetrahydro-2H-indazol-5-ylamine収率 75%

実験手順

8-Bromo-2-methoxy-[1,5]naphthyridine. To a suspension of 6-methoxy-[1,5]naphthyridin-4-ol (8.8 g, 0.050 mol) in DMF (167 mL) was added PBr3 (4.7 mL, 0.050 mol) at 45° C. The suspension became homogeneous and then a suspension formed over 20 min. The mixture was cooled to RT and the solid was filtered and washed with Et2O (100 mL). Further solids precipitated from the filtrate and were collected. Water (50 mL) was added to the solid and the suspension was basified with 1 N NaOH (200 mL). The aqueous layer was extracted with CH2Cl2 (3×250 mL), washed with brine (150 mL), dried (MgSO4) and concentrated. The resulting residue was purified on SiO2 (0-60% EtOAc/hexanes) to provide 8.9 g (75%) of the title compound as a white solid. MS (ESI): exact mass calculated for C9H7BrN2O, 237.97; m/z found, 239.2 [M+H]+. 1H NMR (400 MHz, DMSO-d6): 8.57 (d, J=4.7, 1H), 8.27 (d, J=9.0, 1H), 8.05 (d, J=4.7, 1H), 7.30 (d, J=9.0, 1H), 4.04 (s, 3H).

後処理

  1. customa suspension formed over 20 min
  2. filtrationthe solid was filtered
  3. washwashed with Et2O (100 mL)
  4. customFurther solids precipitated from the filtrate
  5. customwere collected
  6. additionWater (50 mL) was added to the solid
  7. extractionThe aqueous layer was extracted with CH2Cl2 (3×250 mL)
  8. washwashed with brine (150 mL)
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated
  11. customThe resulting residue was purified on SiO2 (0-60% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-397dbc61dd0e48d69c09603928ea3326
出典データセット
uspto-grants-2010_11
特許番号
US07842810B2

反応ノート

読み込み中…