Hydrochloric Acid → (+/-)-3-(6-Methyl-2-p-tolyl-imidazo[1,2-alpha]pyridin-3-yl)-piperidin-2-one

HRID 230272Notes

Reaction equation

HRID 230272 reaction equation
CO[C:3](=[O:32])[CH:4]([C:15]1[N:19]2[CH:20]=[C:21]([CH3:24])[CH:22]=[CH:23][C:18]2=[N:17][C:16]=1[C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=1)[CH2:5][CH2:6][CH2:7][NH:8]S(C(C)(C)C)=O.Cl>CO.CO.CCOC(C)=O>[CH3:24][C:21]1[CH:22]=[CH:23][C:18]2[N:19]([C:15]([CH:4]3[CH2:5][CH2:6][CH2:7][NH:8][C:3]3=[O:32])=[C:16]([C:25]3[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=3)[N:17]=2)[CH:20]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 58763604(+/-)-5-(2-Methyl-propane-2-sulfinylamino)-2-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-yl)-pentanoic acid methyl ester

Product 1

HCID 58763609(+/-)-3-(6-Methyl-2-p-tolyl-imidazo[1,2-alpha]pyridin-3-yl)-piperidin-2-oneYield 77%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

To a magnetically stirred solution of (+/−)-5-(2-methyl-propane-2-sulfinylamino)-2-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-yl)-pentanoic acid methyl ester 44b (0.039 g, 0.0824 mmol) in methanol (3 mL) at room temperature under Ar atmosphere was 5N HCl (1.71 mL). The reaction mixture was stirred for 3 h at room temperature, then concentrated in vacuo. The reaction mixture was treated with 10% aq NaOH solution until basic. After 30 mm, 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 (0.0202 g, 77%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 1.92 (m, 1H), 2.04 (m, 2H), 2.16 (m, 1H), 2.32 (s, 3H), 2.39 (s, 3H), 3.50 (m, 2H), 4.28 (dd, J=6.2, 12.4 Hz, 1H), 6.37 (s, 1H), 7.00 (d, J=10.2 Hz, 1H), 7.24 (d, J=8.0 Hz, 2H), 7.56 (m, 3H). Mass spectrum (m/e) 320 (M+).

Workup

  1. customat room temperature
  2. concentrationconcentrated in vacuo
  3. additionThe reaction mixture was treated with 10% aq NaOH solution until basic
  4. additionAfter 30 mm, water (30 mL) was added
  5. extractionthe aqueous phase was extracted with EtOAc (2×50 mL)
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. concentrationconcentrated in vacuo to the crude product
  8. customThe pure product was obtained by column chromatography over silica gel (EtOAc

Sources & evidence

ORD record
ord-40b763d9eecf4573b21f79b650559f23
Source dataset
uspto-grants-2009_07
Patent number
US07566725B2

Reaction notes

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