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

HRID 519301Notes

Reaction equation

HRID 519301 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.CC(O)=O>[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 109d (500 mg, 1.3 mmol), and 30% formaldehyde (6.5 mmol) in methanol/HOAc (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. It was cooled to room temperature and H2O (20 mL) was added. The mixture was extracted with DCM (50 mL) three times. The combined organic layer was concentrated under reduced pressure and the residue was purified by column chromatography eluting with 30:1 DCM/methanol to afford 109e as a yellow solid (473 mg, 83%). MS: [M+H]+ 392.

Workup

  1. stirringThe mixture was stirred at room temperature for 4 h
  2. temperatureIt was cooled to room temperature
  3. extractionThe mixture was extracted with DCM (50 mL) three times
  4. concentrationThe combined organic layer was concentrated under reduced pressure
  5. customthe residue was purified by column chromatography
  6. washeluting with 30:1 DCM/methanol

Sources & evidence

ORD record
ord-dfc5933c6f384920bc627a46083fce59
Source dataset
uspto-grants-2015_08
Patent number
US09115152B2

Reaction notes

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