Potassium Carbonate → 3-Bromo-2-ethynyl-8-(4-morpholinyl)imidazo[1,2-b]pyridazine

HRID 718585Notes

Reaction equation

HRID 718585 reaction equation
[Br:1][C:2]1[N:6]2[N:7]=[CH:8][CH:9]=[C:10]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[C:5]2=[N:4][C:3]=1[CH:17]=O.[C:19]([O-])([O-])=O.[K+].[K+].[N+](=C(P(=O)(OC)OC)C(=O)C)=[N-]>CO.C(Cl)Cl>[Br:1][C:2]1[N:6]2[N:7]=[CH:8][CH:9]=[C:10]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[C:5]2=[N:4][C:3]=1[C:17]#[CH:19]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 1177288343-Bromo-8-morpholinoimidazo[1,2-b]pyridazine-2-carbaldehydeHCID 136023029(1E)-1-diazo-1-dimethoxyphosphorylpropan-2-one

Product 1

HCID 1177287753-Bromo-2-ethynyl-8-(4-morpholinyl)imidazo[1,2-b]pyridazine

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a suspension of compound 14b (0.78 g, 2.5 mmol) in MeOH (20 mL) was added K2CO3 (1.1 g, 7.5 mmol) and a solution of dimethyl (1-diazo-2-oxopropyl)phosphonate (0.53 g, 2.7 mmol) in MeOH (5 mL). The reaction mixture was stirred at rt overnight, diluted with DCM (200 mL), and washed with water (20 mL) and brine (20 mL). The organic layer was dried over MgSO4, filtered and concentrated. The residue obtained was purified by flash column chromatography on silica gel (0-20% EtOAc/DCM) to give compound 18a as a white solid. 1H-NMR (400 MHz, CDCl3) δ (ppm): 8.13 (d, J=5.56 Hz, 1H), 6.11 (d, J=5.56 Hz, 1H), 3.94-4.01 (m, 4H), 3.86-3.93 (m, 4H), 3.41 (s, 1H).

Workup

  1. washwashed with water (20 mL) and brine (20 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue obtained
  6. customwas purified by flash column chromatography on silica gel (0-20% EtOAc/DCM)

Sources & evidence

ORD record
ord-a848e07fa6b243db9aad7e46b5b4f44e
Source dataset
uspto-grants-2015_11
Patent number
US09193736B2

Reaction notes

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