Sodium cyanoborohydride → (S)-6-Bromo-N-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine

HRID 1024068Notes

Reaction equation

HRID 1024068 reaction equation
Br.[Br:2][C:3]1[CH:4]=[C:5]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:24][CH2:23][NH:22][CH2:21][C@@H:20]3[CH3:25])=[CH:15][N:14]=2)[C:6]2[N:7]([CH:9]=[CH:10][N:11]=2)[N:8]=1.[O:26]1[CH2:29][C:28](=O)[CH2:27]1.[BH3-]C#N.[Na+]>CO.[Cl-].[Cl-].[Zn+2]>[Br:2][C:3]1[CH:4]=[C:5]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:24][CH2:23][N:22]([CH:28]4[CH2:29][O:26][CH2:27]4)[CH2:21][C@@H:20]3[CH3:25])=[CH:15][N:14]=2)[C:6]2[N:7]([CH:9]=[CH:10][N:11]=2)[N:8]=1

Participants

6

Reactant 3

HCID 5003444Sodium cyanoborohydrideHCID 150242543-OxetanoneHCID 86684145(S)-6-Bromo-N-(5-(2-methylpiperazin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine hydrobromide

Product 1

HCID 86684147(S)-6-Bromo-N-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amineYield 22.1%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of (S)-6-bromo-N-(5-(2-methylpiperazin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine hydrobromide 115d (1.05 g, 2.24 mmol), oxetan-3-one (483 mg, 6.7 mmol), and ZnCl2 (914 mg, 6.7 mmol) in methanol (30 mL) was added NaBH3CN (421 mg, 6.7 mmol). The reaction mixture was heated at 50° C. for 14 h and concentrated under reduced pressure. Water (30 mL) was added to the residue and the resulting mixture was extracted with dichloromethane (% X 30 mL). The combined organic phase was dried over anhydrous MgSO4 and filtered. The filtrate was evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 40:1 dichloromethane/methanol to afford 115e as a yellow solid (220 mg, 22%). MS-ESI: [M+H]+ 444.1

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionWater (30 mL) was added to the residue
  3. extractionthe resulting mixture was extracted with dichloromethane (% X 30 mL)
  4. dry with materialThe combined organic phase was dried over anhydrous MgSO4
  5. filtrationfiltered
  6. customThe filtrate was evaporated under reduced pressure
  7. customThe residue was purified by silica-gel column chromatography
  8. washeluting with 40:1 dichloromethane/methanol

Sources & evidence

ORD record
ord-c2528665cb4c47d49ca610b0ce27df51
Source dataset
uspto-grants-2014_05
Patent number
US08722676B2

Reaction notes

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