Acetaldehyde → 5-bromo-3-(5-(1-ethylazetidin-3-yl)pyridin-2-ylamino)-1-methylpyridin-2(1H)-one

HRID 1919048Notes

Reaction equation

HRID 1919048 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.[CH3:21][CH:22]=O.[OH-].[Na+]>CO.C(O)(=O)C>[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]([CH2:21][CH3:22])[CH2:2]3)=[CH:10][N:9]=2)[C:13](=[O:20])[N:14]([CH3:19])[CH:15]=1

Participants

6

Reactant 3

HCID 177AcetaldehydeHCID 14798Sodium HydroxideHCID 580437193-(5-(azetidin-3-yl)pyridin-2-ylamino)-5-bromo-1-methylpyridin-2(1H)-one

Product 1

HCID 580441415-bromo-3-(5-(1-ethylazetidin-3-yl)pyridin-2-ylamino)-1-methylpyridin-2(1H)-oneYield 43%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

To a solution of 3-(5-(azetidin-3-yl)pyridin-2-ylamino)-5-bromo-1-methylpyridin-2(1H)-one 155n (crude, 4.6 mmol) in methanol (50 mL) and acetic acid (5 mL) at 0° C., was added CH3CHO (40% wt in H2O) (10 g, 92 mmol) followed by the addition of NaBH(CH3O)3 (20 g, 92 mmol) in small portions over a period of 1 h. After the reaction was finished, the mixture was adjusted to pH>7 with 2N NaOH. Then the mixture was extracted with DCM (80 mL×3), dried over Na2SO4 and concentrated to get a yellow solid, which was purified on flash column eluting with 50:1 DCM/MeOH containing 0.5% Et3N to afford 250a as a yellow solid (43%, two steps). LCMS: (M+H)+ 364. 1H NMR (500 MHz, DMSO) δ 8.72 (s, 1H), 8.66 (d, J=3, 1H), 8.21 (d, J=3, 1H), 7.68 (dd, J=9, 1H), 7.52 (d, J=2.5, 1H), 7.32 (d, J=9, 1H), 3.54 (m, 6H), 2.99 (m, 2H), 2.42 (m, 2H), 0.89 (t, J=7, 3H).

Workup

  1. extractionThen the mixture was extracted with DCM (80 mL×3)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customto get a yellow solid, which
  5. customwas purified on flash column
  6. washeluting with 50:1 DCM/MeOH containing 0.5% Et3N

Sources & evidence

ORD record
ord-bacc736e634a47e09d05a79d626be251
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

Loading…