Sodium cyanoborohydride → (S)-6-Chloro-4-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)pyridazin-3(2H)-one

HRID 593004Notes

Reaction equation

HRID 593004 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:21][CH2:20][NH:19][CH2:18][C@@H:17]3[CH3:22])=[CH:12][N:11]=2)[C:5](=[O:8])[NH:6][N:7]=1.[O:23]1[CH2:26][C:25](=O)[CH2:24]1.[BH3-]C#N.[Na+]>[Cl-].[Cl-].[Zn+2].CO>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:21][CH2:20][N:19]([CH:25]4[CH2:26][O:23][CH2:24]4)[CH2:18][C@@H:17]3[CH3:22])=[CH:12][N:11]=2)[C:5](=[O:8])[NH:6][N:7]=1

Participants

6

Reactant 3

HCID 5003444Sodium cyanoborohydrideHCID 150242543-OxetanoneHCID 86684485(S)-6-Chloro-4-(5-(2-methylpiperazin-1-yl)pyridin-2-ylamino)pyridazin-3(2H)-one

Product 1

HCID 86684486(S)-6-Chloro-4-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)pyridazin-3(2H)-oneYield 56%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent

Procedure

A 50-mL round-bottomed flask equipped with a magnetic stirrer was charged with 253c (321 mg, 1.0 mmol), 3-oxetanone (142 mg, 2.0 mmol), NaBH3CN (125 mg, 2.0 mmol), ZnCl2 (272 mg, 2.0 mmol), and methanol (10 mL). The mixture was stirred at room temperature overnight and concentrated under reduced pressure. Water (20 mL) was added to the residue and the resulting mixture was extracted with dichloromethane (3×20 mL). The combined organic layer was concentrated under reduced pressure and the residue was purified by silica-gel column chromatography eluting with ethyl acetate to afford 253d (210 mg, 56%) as yellow solid. MS-ESI: [M+H]+ 377.3.

Workup

  1. customA 50-mL round-bottomed flask equipped with a magnetic stirrer
  2. concentrationconcentrated under reduced pressure
  3. additionWater (20 mL) was added to the residue
  4. extractionthe resulting mixture was extracted with dichloromethane (3×20 mL)
  5. concentrationThe combined organic layer was concentrated under reduced pressure
  6. customthe residue was purified by silica-gel column chromatography
  7. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-d02c575c173e44b9b028542636dc8b37
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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