Sodium hydride → HCID 71534334, compound

HRID 1755430Notes

Reaction equation

HRID 1755430 reaction equation
Br[C:2]1[C:3]2[N:4]([CH:9]=[CH:10][N:11]=2)[N:5]=[C:6]([Cl:8])[CH:7]=1.[CH3:12][O:13][C:14]1[CH:15]=[CH:16][C:17]([NH2:22])=[N:18][C:19]=1[O:20][CH3:21].[H-].[Na+]>CN(C=O)C>[Cl:8][C:6]1[CH:7]=[C:2]([NH:22][C:17]2[CH:16]=[CH:15][C:14]([O:13][CH3:12])=[C:19]([O:20][CH3:21])[N:18]=2)[C:3]2[N:4]([CH:9]=[CH:10][N:11]=2)[N:5]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 467391485,6-Dimethoxypyridin-2-amineHCID 468352698-Bromo-6-chloroimidazo(1,2-b)pyridazine

Product 1

HCID 71534334HCID 71534334, compoundYield 91.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 8-bromo-6-chloroimidazo[1,2-b]pyridazine (2 g, 8.6 mmol) and 5,6-dimethoxypyridin-2-amine (1.39 g, 9.03 mmol) in DMF (72 ml) was cooled to 0° C. To the mixture was added sodium hydride (1.1 g, 27.5 mmol, 60% dispersion in mineral oil). The reaction was stirred for 10 min then warmed to room temperature. After 15 h the reaction was quenched with saturated sodium bicarbonate solution, and then diluted with water and EtOAc. An insoluble solid was filtered off. The filtrate was separated and the aqueous phase was washed with EtOAc. The combined organic extracts were concentrated in vacuo and the residue obtained was crystallized from methanol to give 6-chloro-N-(5,6-dimethoxypyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (2.4 g, 7.85 mmol, 91.2%) as light brown needles. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 8.26 (br. s., 1H) 7.95 (s, 1H) 7.81 (s, 1H) 7.55 (s, 1H) 7.15 (d, J=7.93 Hz, 1H) 6.58 (d, J=8.31 Hz, 1H) 4.12 (s, 3H) 3.89 (s, 3H); LC/MS: 305.9 [MH]+.

Workup

  1. temperaturethen warmed to room temperature
  2. customAfter 15 h the reaction was quenched with saturated sodium bicarbonate solution
  3. additiondiluted with water and EtOAc
  4. filtrationAn insoluble solid was filtered off
  5. customThe filtrate was separated
  6. washthe aqueous phase was washed with EtOAc
  7. concentrationThe combined organic extracts were concentrated in vacuo
  8. customthe residue obtained
  9. customwas crystallized from methanol

Sources & evidence

ORD record
ord-6fd3233990ea48598cf851fcd2356294
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

Loading…