Formaldehyde → (R)-5-Bromo-3-(5-(2,4-dimethylpiperazin-1-yl)pyridin-2-ylamino)-1-methylpyridin-2(1H)-one

HRID 1026463Notes

Reaction equation

HRID 1026463 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][NH:20][CH2:19][C@H:18]3[CH3:23])=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.C=O.[BH3-][C:27]#N.[Na+].O>CO.C(O)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][N:20]([CH3:27])[CH2:19][C@H:18]3[CH3:23])=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 962WaterHCID 5003444Sodium cyanoborohydrideHCID 86683719(R)-5-Bromo-1-methyl-3-(5-(2-methylpiperazin-1-yl)pyridin-2-ylamino)pyridin-2(1H)-one

Product 1

HCID 86683720(R)-5-Bromo-3-(5-(2,4-dimethylpiperazin-1-yl)pyridin-2-ylamino)-1-methylpyridin-2(1H)-oneYield 92.7%

Reagents, catalysts & solvents 1

HCID 10129899Acetic acid methanolSolvent

Procedure

A mixture of 115d (500 mg, 1.3 mmol) and 30% formaldehyde (650 mg, 6.5 mmol) in methanol/acetic acid (30 mL/3 mL) was stirred at room temperature for 5 minutes, followed by the addition of NaBH3CN (120 mg, 1.9 mmol). The mixture was stirred at room temperature for 4 h. water (20 mL) was added and the resulting mixture was concentrated under reduced pressure. The residue was extracted with dichloromethane (3×30 mL). The combined organic layer was concentrated under reduced pressure and the residue was purified by silica-gel column chromatography eluting with 30:1 dichloromethane/methanol to afford 115e as a yellow solid (473 mg, 92%). MS-ESI: [M+H]+ 392.

Workup

  1. additionwas added
  2. concentrationthe resulting mixture was concentrated under reduced pressure
  3. extractionThe residue was extracted with dichloromethane (3×30 mL)
  4. concentrationThe combined organic layer was concentrated under reduced pressure
  5. customthe residue was purified by silica-gel column chromatography
  6. washeluting with 30:1 dichloromethane/methanol

Sources & evidence

ORD record
ord-1945f26e6b324d49b50401360fd320df
Source dataset
uspto-grants-2014_05
Patent number
US08729072B2

Reaction notes

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