Pyridine → 2-[(4-ethoxyphenyl)methyl]-N,N-diethyl-3-[(5-nitro-2-thienyl)methyl]-3H-imidazo[4,5-b]pyridine-6-carboxamide

HRID 1796522Notes

Reaction equation

HRID 1796522 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]([CH2:13][CH3:14])[CH2:11][CH3:12])=[O:9])=[CH:4][C:3]=1[NH:15][C:16](=O)[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH3:26])=[CH:20][CH:19]=1.[N+:28]([C:31]1[S:35][C:34]([CH:36]=O)=[CH:33][CH:32]=1)([O-:30])=[O:29].N1C=CC=CC=1>ClC(Cl)C.C(O)(=O)C>[CH2:25]([O:24][C:21]1[CH:22]=[CH:23][C:18]([CH2:17][C:16]2[N:1]([CH2:36][C:34]3[S:35][C:31]([N+:28]([O-:30])=[O:29])=[CH:32][CH:33]=3)[C:2]3=[N:7][CH:6]=[C:5]([C:8]([N:10]([CH2:13][CH3:14])[CH2:11][CH3:12])=[O:9])[CH:4]=[C:3]3[N:15]=2)=[CH:19][CH:20]=1)[CH3:26]

Participants

6

Reactant 3

HCID 1049Pyridine2×HCID 782815-Nitrothiophene-2-carboxaldehyde2×HCID 221813586-amino-5-[[(4-ethoxyphenyl)acetyl]amino]-N,N-diethyl-3-pyridinecarboxamide

Product 1

HCID 221813252-[(4-ethoxyphenyl)methyl]-N,N-diethyl-3-[(5-nitro-2-thienyl)methyl]-3H-imidazo[4,5-b]pyridine-6-carboxamide

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of 6-amino-5-[[(4-ethoxyphenyl)acetyl]amino]-N,N-diethyl-3-pyridinecarboxamide (30 mg, 0.08 mmol) in dichloroethane (0.5 mL) and acetic acid (0.5 mL) at room temperature was added 5-nitro-2-thiophenecarboxaldehyde (19 mg, 0.12 mmol). The mixture was stirred for 4.5 hours. BH3. pyridine (8.2 μL, 0.08 mmol) was added and the reaction brought to 84° C. After stirring overnight, the mixture was cooled to room temperature and 5-nitro-2-thiophenecarboxaldehyde (19 mg, 0.12 mmol) was added. The mixture was stirred for 5 hours. BH3.pyridine (8.2 μL, 0.08 mmol) was added and the reaction brought to 84° C. After stirring overnight, the reaction was quenched with 1 M NaOH aqueous solution (20 mL) and extracted with EtOAc (20 mL). The aqueous phase was back-extracted with additional dichloromethane (2×20 mL). The organic phases were combined, dried with MgSO4, filtered and concentrated in vacuo. The residue was purified using silica gel flash chromatography ([3% MEOH+0.5% NH4OH aq] in CH2Cl2) to provide the title compound 2-[(4-ethoxyphenyl)methyl]-N,N-diethyl-3-[(5-nitro-2-thienyl)methyl]-3H-imidazo[4,5-b]pyridine-6-carboxamide (purity: >84% at 215 nm, >81% at 254 nm, >68% at 280 nm). 1H-NMR (400 MHz, CDCl3): δ 1.23 (m, 6H), 1.40 (t, J=6.8 Hz, 3H), 3.36 (br s, 2H), 3.60 (br s, 2H), 3.98 (q, J=6.8 Hz, 2H), 4.29 (s, 2H), 4.84 (s, 2H), 6.80 (d, J=8.6 Hz, 2H), 7.07 (d, J=8.6 Hz, 2H), 7.66 (d, J=4.1 Hz, 1H), 7.77 (d, J=4.1 Hz, 1H), 8.03 (d, J=2.0 Hz, 1H), 8.03 (d, J=2.0 Hz, 1H). MS (ESI) (M+H)+: 494.

Workup

  1. custombrought to 84° C
  2. stirringAfter stirring overnight
  3. stirringThe mixture was stirred for 5 hours
  4. custombrought to 84° C
  5. stirringAfter stirring overnight
  6. customthe reaction was quenched with 1 M NaOH aqueous solution (20 mL)
  7. extractionextracted with EtOAc (20 mL)
  8. extractionThe aqueous phase was back-extracted with additional dichloromethane (2×20 mL)
  9. dry with materialdried with MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified

Sources & evidence

ORD record
ord-1d060a315f7a495995739e9be97e85d2
Source dataset
uspto-grants-2006_04
Patent number
US07030139B2

Reaction notes

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