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

HRID 1518005노트

반응식

HRID 1518005 반응식
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

참가 물질

5

반응물 4

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

생성물 1

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

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-d843e9bad8954167999abd8ab010fce3
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08232391B2

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