Boric Acid → 1-Methyl-5-(pyridin-2-yl)-1,2,3,4-tetrahydropyrimido[4,5-c]pyridazine

HRID 717573Notes

Reaction equation

HRID 717573 reaction equation
[CH3:1][N:2]1[C:7]2[N:8]=[CH:9][N:10]=[C:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)[C:6]=2[CH2:5][CH:4]=[N:3]1.[BH4-].[Na+].B(O)(O)O>C1COCC1>[CH3:1][N:2]1[C:7]2[N:8]=[CH:9][N:10]=[C:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)[C:6]=2[CH2:5][CH2:4][NH:3]1

Participants

5

Reactant 3

HCID 7628Boric AcidHCID 4311764Sodium borohydrideHCID 898158061-Methyl-5-(pyridin-2-yl)-1,4-dihydropyrimido[4,5-c]pyridazine

Product 1

HCID 898158291-Methyl-5-(pyridin-2-yl)-1,2,3,4-tetrahydropyrimido[4,5-c]pyridazineYield 34.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 1-methyl-5-(pyridin-2-yl)-1,4-dihydropyrimido[4,5-c]pyridazine (100 mg) in dry THF (5.0 mL), sodium borohydride (84 mg) was slowly added, followed by boric acid (137 mg) under nitrogen atmosphere at 0° C. The reaction mixture was stirred at room temperature for 2 hours and solvents were removed under reduced pressure. The resulting oil was diluted with dichloromethane (50 mL), washed with 10% NaHCO3 (10 mL) and brine (10 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated to give a residue which was purified by column chromatography using MeOH/CHCl3 (0.5:9.5) as eluent to afford 1-methyl-5-(pyridin-2-yl)-1,2,3,4-tetrahydropyrimido[4,5-c]pyridazine (35 mg) as white solid. 1H NMR (DMSO-d6): δ 2.92-2.93 (m, 4H), 3.22 (s, 3H), 5.49 (t, 1H), 7.41-7.44 (t, 1H), 7.90-7.92 (m, 2H), 8.38 (s, 1H), 8.62-8.64 (d, 1H).

Workup

  1. customsolvents were removed under reduced pressure
  2. additionThe resulting oil was diluted with dichloromethane (50 mL)
  3. washwashed with 10% NaHCO3 (10 mL) and brine (10 mL)
  4. dry with materialThe organic layer was dried over anhydrous Na2SO4
  5. concentrationconcentrated
  6. customto give a residue which
  7. customwas purified by column chromatography

Sources & evidence

ORD record
ord-9952a0fed33f4e2eaaffeecd6c86a426
Source dataset
uspto-grants-2015_11
Patent number
US09193725B2

Reaction notes

Loading…