Acetic Acid → 5-Bromo-1-methyl-3-(5-(1-methylazetidin-3-yloxy)pyridin-2-ylamino)pyridin-2(1H)-one

HRID 592871Notes

Reaction equation

HRID 592871 reaction equation
Cl.[NH:2]1[CH2:5][CH:4]([O:6][C:7]2[CH:8]=[CH:9][C:10]([NH:13][C:14]3[C:15](=[O:22])[N:16]([CH3:21])[CH:17]=[C:18]([Br:20])[CH:19]=3)=[N:11][CH:12]=2)[CH2:3]1.C=O.[C:25](O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CO>[Br:20][C:18]1[CH:19]=[C:14]([NH:13][C:10]2[CH:9]=[CH:8][C:7]([O:6][CH:4]3[CH2:5][N:2]([CH3:25])[CH2:3]3)=[CH:12][N:11]=2)[C:15](=[O:22])[N:16]([CH3:21])[CH:17]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 866612483-(5-(Azetidin-3-yloxy)pyridin-2-ylamino)-5-bromo-1-methylpyridin-2(1H)-one Hydrochloride

Product 1

HCID 580442285-Bromo-1-methyl-3-(5-(1-methylazetidin-3-yloxy)pyridin-2-ylamino)pyridin-2(1H)-oneYield 80%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 206e (1.24 g, 3.2 mmol), 37% aqueous formaldehyde solution (15 mL), acetic acid (1 mL), and NaBH(OAc)3 (1.36 g, 6.4 mmol) in methanol (10 mL) was stirred at room temperature for 4 h. The solvent was evaporated in vacuo and the residue was extracted with ethyl acetate (3×20 mL). The combined extract was dried over sodium sulfate and concentrated under reduced pressure. The residue was purified on reverse-phase Combiflash to afford 206f (940 mg, 80%). MS-ESI: [M+H]+ 365.

Workup

  1. customThe solvent was evaporated in vacuo
  2. extractionthe residue was extracted with ethyl acetate (3×20 mL)
  3. extractionThe combined extract
  4. dry with materialwas dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified on reverse-phase Combiflash

Sources & evidence

ORD record
ord-dc58c14808f3456fa877b1d5bf126a58
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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