Ammonium Chloride → Tert-butyl 3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenylcarbamate

HRID 570324Notes

Reaction equation

HRID 570324 reaction equation
C(Cl)(=O)C(Cl)=O.[N:7]1[CH:8]=[C:9]([C:16]([OH:18])=O)[N:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=12.[NH2:19][C:20]1[CH:21]=[C:22]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH:23]=[CH:24][C:25]=1[CH3:26].[NH4+].[Cl-]>ClCCl.CN(C=O)C.CCN(C(C)C)C(C)C>[N:7]1[CH:8]=[C:9]([C:16]([NH:19][C:20]2[CH:21]=[C:22]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:32])([CH3:31])[CH3:33])[CH:23]=[CH:24][C:25]=2[CH3:26])=[O:18])[N:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=12

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 65578Oxalyl chlorideHCID 73142Imidazo(1,2-a)pyridine-3-carboxylic acidHCID 246997865-(Boc-amino)-2-methylaniline

Product 1

HCID 71280675Tert-butyl 3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenylcarbamate

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×HCID 81531DiisopropylethylamineSolvent

Procedure

Oxalyl chloride (10 mL) was added dropwise to a stirred solution of imidazo[1,2-a]pyridine-3-carboxylic acid (1) (3 g, 18.5 mmol) in dry dichloromethane (100 mL) and a few drops of DMF. The resulting solution was stirred at room temperature for 5 hours before it was evaporated to dryness and fresh dichloromethane was added to the resulting acid chloride to make a suspension. In a separate flask, tert-butyl 3-amino-4-methylphenylcarbamate (65) (4.5 g, 20.3 mmol) and DIEA (10 mL) was dissolved in dichloromethane (100 mL) and the above acid chloride solution was added slowly. The resulting solution was stirred overnight at room temperature. Saturated NH4Cl was added to the reaction solution and the phases were separated. The organic layer was dried over Na2SO4 and filtered. After evaporation, the residue was purified over silica gel column using hexane and EtOAc to give tert-butyl 3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenylcarbamate (66) as a slightly yellow solid.

Workup

  1. customwas evaporated to dryness and fresh dichloromethane
  2. additionwas added to the resulting acid chloride
  3. stirringThe resulting solution was stirred overnight at room temperature
  4. customthe phases were separated
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. customAfter evaporation
  8. customthe residue was purified over silica gel column

Sources & evidence

ORD record
ord-7de9446bf9b14785b92ff0a9beb3e6bd
Source dataset
uspto-grants-2015_05
Patent number
US09023839B2

Reaction notes

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