Water → (+/-)-1-Methyl-3-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-yl)-piperidin-2-one

HRID 858898

Reaction equation

HRID 858898 reaction equation
CO[C:3](=[O:26])[CH:4]([C:9]1[N:13]2[CH:14]=[C:15]([CH3:18])[CH:16]=[CH:17][C:12]2=[N:11][C:10]=1[C:19]1[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=1)[CH2:5][CH2:6][CH:7]=O.[CH3:27][NH2:28].[BH4-].[Na+].O>CO.CO.CCOC(C)=O>[CH3:27][N:28]1[CH2:7][CH2:6][CH2:5][CH:4]([C:9]2[N:13]3[CH:14]=[C:15]([CH3:18])[CH:16]=[CH:17][C:12]3=[N:11][C:10]=2[C:19]2[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=2)[C:3]1=[O:26]

Participants

7

Reactant 4

HCID 962WaterHCID 6329MethylamineHCID 4311764Sodium borohydrideHCID 587635832-(6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-yl)-5-oxo-pentanoic acid methyl ester

Product 1

HCID 11325081(+/-)-1-Methyl-3-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-yl)-piperidin-2-oneYield 35.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

To a magnetically stirred solution of (±)-2-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-yl)-5-oxo-pentanoic acid methyl ester 35c (0.085 g, 0.253 mmol) in methanol (1 mL) at room temperature under Ar atmosphere was added a 40% aqueous solution of methyl amine (MeNH2) (0.021 mL, 0.253 mmol). The reaction mixture was stirred for 1 h at room temperature. NaBH4 (0.019 g, 0.506 mmol) was added at room temperature. After 30 min, water (30 mL) was added, and the aqueous phase was extracted with EtOAc (2×50 mL). The combined organic layers were dried (MgSO4), and concentrated in vacuo to the crude product. The pure product was obtained by column chromatography over silica gel (EtOAc, then 4:96 MeOH/EtOAc as eluent) which gave the title compound (0.03 g, 31%) as a white solid. The combined organic layers were washed with water, dried (MgSO4), and concentrated in vacuo to the crude product. 1H NMR (400 MHz, CDCl3) δ 1.99 (m, 3H), 2.11 (m, 1H), 2.31 (s, 3H), 2.38 (s, 3H), 3.05 (s, 3H), 3.41 (m, 1H), 3.53 (m, 1H), 4.25 (m, 1H), 6.99 (d, J=9.1 Hz, 1H), 7.22 (m, 3H), 7.46 (s, 1H), 7.53 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 18.9, 21.5, 23.1, 26.1, 35.4, 39.7, 50.3, 117.4, 119.1, 121.5, 121.7, 127.0, 129.1, 129.3, 132.4, 137.5, 143.9, 144.4, 168.7. Mass spectrum m/e 335 (M+).

Workup

  1. waitAfter 30 min
  2. extractionthe aqueous phase was extracted with EtOAc (2×50 mL)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. concentrationconcentrated in vacuo to the crude product
  5. customThe pure product was obtained by column chromatography over silica gel (EtOAc

Sources & evidence

ORD record
ord-7a0e285c2ce54395bd4b2c4fd3f69c6c
Source dataset
uspto-grants-2006_12
Patent number
US07148353B2

Linked notes

Loading…