Formaldehyde → 5-Bromo-1-methyl-3-(5-(1-methylazetidin-3-yl)pyridin-2-ylamino)pyridine-2(1H)-one

HRID 592964Notes

Reaction equation

HRID 592964 reaction equation
[NH:1]1[CH2:4][CH:3]([C:5]2[CH:6]=[CH:7][C:8]([NH:11][C:12]3[C:13](=[O:20])[N:14]([CH3:19])[CH:15]=[C:16]([Br:18])[CH:17]=3)=[N:9][CH:10]=2)[CH2:2]1.C=O.[BH3-][C:24]#N.[Na+].C(OCC)C>CO.[Cl-].[Zn+2].[Cl-].O>[Br:18][C:16]1[CH:17]=[C:12]([NH:11][C:8]2[CH:7]=[CH:6][C:5]([CH:3]3[CH2:4][N:1]([CH3:24])[CH2:2]3)=[CH:10][N:9]=2)[C:13](=[O:20])[N:14]([CH3:19])[CH:15]=1

Participants

8

Reactant 4

HCID 712FormaldehydeHCID 3283Diethyl EtherHCID 5003444Sodium cyanoborohydrideHCID 580437193-(5-(azetidin-3-yl)pyridin-2-ylamino)-5-bromo-1-methylpyridin-2(1H)-one

Product 1

HCID 580440835-Bromo-1-methyl-3-(5-(1-methylazetidin-3-yl)pyridin-2-ylamino)pyridine-2(1H)-oneYield 83%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A mixture of 239b (469 mg, 1.4 mmol), 37% aqueous formaldehyde (4.0 g, 50 mmol), NaBH3CN (261 mg, 4.2 mmol), and 1M zinc chloride in ethoxyethane (4 mL, 4.2 mmol) in methanol (40 mL) was stirred at room temperature for 2 hours. The mixture was added to water (20 mL) and concentrated under reduced pressure. The residue was extracted with dichloromethane (3×50 mL). The combined organic layer was concentrated under reduced pressure and the residue was purified by silica-gel column chromatography eluting with 10:1 methylene chloride/methanol to afford 239c as a yellow solid (300 mg, 83%). MS-ESI: [M+H]+ 349.

Workup

  1. concentrationconcentrated under reduced pressure
  2. extractionThe residue was extracted with dichloromethane (3×50 mL)
  3. concentrationThe combined organic layer was concentrated under reduced pressure
  4. customthe residue was purified by silica-gel column chromatography
  5. washeluting with 10:1 methylene chloride/methanol

Sources & evidence

ORD record
ord-f81adc3649dc4ce0be7b7cba437ef97f
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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