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

HRID 885664Notes

Reaction equation

HRID 885664 reaction equation
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

Participants

5

Reactant 4

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

Product 1

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

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-f376d8fb5a2a4a2fb6b210f440ea1b68
Source dataset
uspto-grants-2012_08
Patent number
US08242275B2

Reaction notes

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