Diethyl Pyrocarbonate → Tert-butyl 4-({[(5-amino-6-chloro-2-ethylimidazo[1,2-a]pyridin-8-yl)carbonyl]amino}methyl)piperidine-1-carboxylate

HRID 965800Notes

Reaction equation

HRID 965800 reaction equation
[NH2:1][C:2]1[N:7]2[CH:8]=[C:9]([CH2:11][CH3:12])[N:10]=[C:6]2[C:5]([C:13]([OH:15])=O)=[CH:4][C:3]=1[Cl:16].[NH2:17][CH2:18][CH:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1.CCOC(OC(OCC)=O)=O.C(N(C(C)C)CC)(C)C>CN(C)C=O>[NH2:1][C:2]1[N:7]2[CH:8]=[C:9]([CH2:11][CH3:12])[N:10]=[C:6]2[C:5]([C:13]([NH:17][CH2:18][CH:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]2)=[O:15])=[CH:4][C:3]=1[Cl:16]

Participants

6

Reactant 4

HCID 3051Diethyl PyrocarbonateHCID 81531DiisopropylethylamineHCID 7368171-Boc-4-(aminomethyl)piperidineHCID 222364965-Amino-6-chloro-2-ethylimidazo[1,2-a]pyridine-8-carboxylic acid

Product 1

HCID 22236502Tert-butyl 4-({[(5-amino-6-chloro-2-ethylimidazo[1,2-a]pyridin-8-yl)carbonyl]amino}methyl)piperidine-1-carboxylateYield 90%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 5-amino-6-chloro-2-ethylimidazo[1,2-a]pyridine-8-carboxylic acid (Example 4, Step 2, 10.00 g, 41.72 mmol), tert-butyl 4-(aminomethyl)piperidine-1-carboxylate (J. Prugh, L. A. Birchenough and M. S. Egbertson, Synth. Commun., 1992, 22, 2357-60, 15.20 g, 70.93 mmol), DEPC (10.76 mL, 70.93 mmol) and diisopropylethylamine (18.17 mL, 104.4 mmol) in N,N-dimethylformamide (267 mL) was stirred at room temperature for 43 h. The solvent was removed by evaporation. The residue was basified with aqueous sodium bicarbonate (40 mL), and extracted with dichloromethane (5×100 mL). The combined extract was washed with brine, dried over magnesium sulfate, and concentrated in vacuo. Flash chromatography of the residue eluting with dichloromethane/methanol (100:1 to 20:1) afforded 19.08 g (90%) of the title compound as a yellow oil.

Workup

  1. customThe solvent was removed by evaporation
  2. extractionextracted with dichloromethane (5×100 mL)
  3. extractionThe combined extract
  4. washwas washed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. washFlash chromatography of the residue eluting with dichloromethane/methanol (100:1 to 20:1)

Sources & evidence

ORD record
ord-596ddcdc5866481d803d4f6ad3a73b91
Source dataset
uspto-grants-2005_10
Patent number
US06951867B2

Reaction notes

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