Diisopropylethylamine → Ethyl 5-(4-(but-3-en-1-yl)-4-methylpiperidin-1-yl)-6-(2-methoxy-2-oxoacetyl)-7-methylimidazo[1,2-a]pyridine-2-carboxylate

HRID 1481969Notes

Reaction equation

HRID 1481969 reaction equation
Cl[C:2]1[N:7]2[CH:8]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[N:10]=[C:6]2[CH:5]=[C:4]([CH3:16])[C:3]=1[C:17](=[O:22])[C:18]([O:20][CH3:21])=[O:19].CC[N:25]([CH:29]([CH3:31])C)[CH:26]([CH3:28])C.C([O-])(O)=O.[Na+]>>[CH2:4]([C:5]1([CH3:6])[CH2:28][CH2:26][N:25]([C:2]2[N:7]3[CH:8]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[N:10]=[C:6]3[CH:5]=[C:4]([CH3:16])[C:3]=2[C:17](=[O:22])[C:18]([O:20][CH3:21])=[O:19])[CH2:29][CH2:31]1)[CH2:3][CH:17]=[CH2:18]

Participants

4

Reactant 3

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 117631349Ethyl5-chloro-6-(2-methoxy-2-oxoacetyl)-7-methylimidazo[1,2-a]pyridine-2-carboxylate

Product 1

HCID 118308840Ethyl 5-(4-(but-3-en-1-yl)-4-methylpiperidin-1-yl)-6-(2-methoxy-2-oxoacetyl)-7-methylimidazo[1,2-a]pyridine-2-carboxylate

Procedure

A solution of ethyl 5-chloro-6-(2-methoxy-2-oxoacetyl)-7-methylimidazo[1,2-a]pyridine-2-carboxylate (0.40 g, 1.23 mmol, 1 equiv), DIPEA (0.52 mL, 2.96 mmol, 2.4 equiv), and 4-(but-3-en-1-yl)-4-methylpiperidine, HCl (0.23 g, 1.23 mmol, 1 equiv). After 2 h, the reaction was added to saturated aqueous NaHCO3 and extracted with EtOAc (×3). The combined EtOAc extracts were dried (Na2SO4) and concentrated in vacuo. The crude product was purified by flash column chromatography (0-100% EtOAc/hex) to provide the product (0.44, 81%) as a viscous yellow oil that slowly crystallized. 1H NMR (400 MHz, CDCl3) δ 8.28-8.13 (m, 1H), 7.37 (br. s., 1H), 5.96-5.78 (m, 1H), 5.08 (d, J=17.6 Hz, 1H), 5.00 (d, J=10.5 Hz, 1H), 4.57-4.43 (m, 2H), 3.97 (s, 3H), 3.62-3.28 (m, 2H), 3.01-2.87 (m, 2H), 2.34 (d, J=0.8 Hz, 3H), 2.14-2.04 (m, 2H), 1.62-1.38 (m, 9H), 1.14-0.99 (m, 3H); LCMS (ESI, M+1): 442.25.

Workup

  1. extractionextracted with EtOAc (×3)
  2. dry with materialThe combined EtOAc extracts were dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by flash column chromatography (0-100% EtOAc/hex)
  5. customto provide the product (0.44, 81%) as a viscous yellow oil that
  6. customslowly crystallized

Sources & evidence

ORD record
ord-f2618922161f44748b11d177dc45edf0
Source dataset
uspto-grants-2016_08
Patent number
US09409922B2

Reaction notes

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