Sodium cyanoborohydride → 5-Bromo-1-methyl-3-(4-(1-(oxetan-3-yl)piperidin-4-yl)phenylamino)-pyrazin-2(1H)-one

HRID 1919007Notes

Reaction equation

HRID 1919007 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[CH:13][CH:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[O:23]1[CH2:26][C:25](=O)[CH2:24]1.C([BH3-])#N.[Na+]>CO.[Cl-].[Zn+2].[Cl-]>[Br:1][C:2]1[N:3]=[C:4]([NH:10][C:11]2[CH:12]=[CH:13][C:14]([CH:17]3[CH2:22][CH2:21][N:20]([CH:25]4[CH2:26][O:23][CH2:24]4)[CH2:19][CH2:18]3)=[CH:15][CH:16]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1

Participants

6

Reactant 3

HCID 5003444Sodium cyanoborohydrideHCID 150242543-OxetanoneHCID 580437455-Bromo-1-methyl-3-(4-(piperidin-4-yl)phenylamino)pyrazin-2(1H)-one

Product 1

HCID 670161765-Bromo-1-methyl-3-(4-(1-(oxetan-3-yl)piperidin-4-yl)phenylamino)-pyrazin-2(1H)-oneYield 60%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent2×

Conditions

Temperature
48 °C

Procedure

A 100-mL sealed tube with a magnetic stirrer was purged with nitrogen and charged with 214a (390 mg, 1.08 mmol), oxetan-3-one (800 mg, 11 mmol) and methanol (10 mL). A suspension of sodium cyanoborohydride (208 mg, 3.3 mmol) and zinc chloride (225 mg, 1.65 mmol) in methanol (10 mL) was added, and the reaction was heated at 48° C. for 12 hours. After this time, the reaction mixture was concentrated, and the residue was partitioned between ethyl acetate (50 mL) and 10% aqueous potassium carbonate (10 mL). The aqueous layer was extracted with ethyl acetate (3×30 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by column chromatography (silica, 60:35:5 methylene chloride/diethyl ethyl/methanol) to afford a 60% yield (270 mg) of 5-bromo-1-methyl-3-(4-(1-(oxetan-3-yl)piperidin-4-yl)phenylamino)pyrazin-2(1H)-one (214b) as a yellow solid: MS (ESI+) m/z 421.2 (M+H).

Workup

  1. customA 100-mL sealed tube with a magnetic stirrer
  2. customwas purged with nitrogen
  3. additionwas added
  4. concentrationAfter this time, the reaction mixture was concentrated
  5. customthe residue was partitioned between ethyl acetate (50 mL) and 10% aqueous potassium carbonate (10 mL)
  6. extractionThe aqueous layer was extracted with ethyl acetate (3×30 mL)
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by column chromatography (silica, 60:35:5 methylene chloride/diethyl ethyl/methanol)

Sources & evidence

ORD record
ord-930da94558cc4f839dadd9e439de2c20
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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