2-Vinylpyridine → HCID 131724947, compound

HRID 2183523Notes

Reaction equation

HRID 2183523 reaction equation
Br[N:2]1[C:6](=O)[CH2:5][CH2:4]C1=O.[CH3:9][C:10]1[O:14][N:13]=[C:12]([C:15]2[N:19]3[N:20]=[C:21]([O:28][CH2:29][C:30]4[CH:31]=[N:32][C:33]([CH:36]=[CH2:37])=[CH:34][CH:35]=4)[C:22]4[C:27]([C:18]3=[N:17][N:16]=2)=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH:11]=1.[OH-:38].[Na+].C(C1C=CC=CN=1)=C.N1CCC1>CN(C=O)C.O.CC(O)=O>[N:2]1([CH2:37][CH:36]([C:33]2[CH:34]=[CH:35][C:30]([CH2:29][O:28][C:21]3[C:22]4[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:18]4=[N:17][N:16]=[C:15]([C:12]5[CH:11]=[C:10]([CH3:9])[O:14][N:13]=5)[N:19]4[N:20]=3)=[CH:31][N:32]=2)[OH:38])[CH2:4][CH2:5][CH2:6]1

Participants

9

Reactant 5

HCID 75212-VinylpyridineHCID 10422AzetidineHCID 14798Sodium HydroxideHCID 67184N-bromobutanimideHCID 131724946HCID 131724946, compound

Product 1

HCID 131724947HCID 131724947, compoundYield 1%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

N-Bromosuccinimide (254 mg, 1.42 mmol) was added to a stirred solution of 3-(5-methylisoxazol-3-yl)-6-(6-vinylpyridin-3-ylmethoxy)-[1,2,4]triazolo[3,4-α]phthalazine (500 mg, 1.30 mmol) in DMF (70 ml), H2O (10 ml) and AcOH (0.1 ml) and the resulting solution stirred at room temperature for 90 min and then 4 N NaOH (3 ml) was added. The mixture was concentrated under reduced pressure and then taken up in CH2Cl2 (100 ml), dried and concentrated. The mixture was purified by column chromatography on silica using 2% MeOH/CH2Cl2 containing 1% NH3 as eluent to yield a 1:1 mixture of the vinylpyridine and the epoxide, m/z (ES+) 401 (M+H+), which was used without further purification. The crude residue was taken up in DMF (5 ml) in a sealed tube and azetidine (126 μl, 1.87 mmol) was added. The reaction was heated at 80° C. for 4 h. The reaction mixture was concentrated under reduced pressure and then taken up in MeOH/CH2Cl2, dry loaded onto silica and purified by column chromatography on silica using 8% MeOH/CH2Cl2 containing 1% NH3 as eluent. The fractions containing the correct compound were concentrated under reduced pressure and further purified on a prep. plate eluting with 7% MeOH/CH2Cl2 containing 1% NH3 to yield the desired phthalazine (4.9 mg, 1%). 1H NMR (400 MHz, CDCl3) δ 8.82 (1H, s), 8.64 (1H, d, J=7.4 Hz), 8.21 (1H, d, J=7.4 Hz), 8.06 (1H, d, J=7.4 Hz), 7.95 (1H, t, J=7.4 Hz), 7.80 (1H, t, J=7.4 Hz), 7.55 (1H, d, J=7.4 Hz), 6.84 (1H, s), 5.68 (2H, s), 4.68 (1H, dd, J=7.7, 3.5 Hz), 3.38-3.23 (4H, m). 2.87 (1H, dd, J=10.9, 3.5 Hz), 2.70 (1H, dd, J=10.9, 7.7 Hz), 2.60 (3H, s), 2.10 (2H, quintet, J=6.3 Hz). m/z (ES+) 457 (M+H+).

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customdried
  3. concentrationconcentrated
  4. customThe mixture was purified by column chromatography on silica using 2% MeOH/CH2Cl2 containing 1% NH3 as eluent
  5. customto yield
  6. customthe epoxide, m/z (ES+) 401 (M+H+), which was used without further purification
  7. customThe crude residue was taken up in DMF (5 ml) in a sealed tube
  8. temperatureThe reaction was heated at 80° C. for 4 h
  9. concentrationThe reaction mixture was concentrated under reduced pressure
  10. customdry loaded onto silica
  11. custompurified by column chromatography on silica using 8% MeOH/CH2Cl2 containing 1% NH3 as eluent
  12. additionThe fractions containing the correct compound
  13. concentrationwere concentrated under reduced pressure
  14. customfurther purified on a prep
  15. washplate eluting with 7% MeOH/CH2Cl2 containing 1% NH3

Sources & evidence

ORD record
ord-8c7f1a6642554dd8b3619f9f181d470d
Source dataset
uspto-grants-2005_05
Patent number
US06900209B2

Reaction notes

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