2-(4-ethoxyphenyl)acetyl Chloride → HCID 22181416, compound

HRID 1796524Notes

Reaction equation

HRID 1796524 reaction equation
[CH:1]1([CH2:4][NH:5][C:6]2[C:11]([NH2:12])=[CH:10][C:9]([N+:13]([O-:15])=[O:14])=[CH:8][N:7]=2)[CH2:3][CH2:2]1.[CH2:16]([O:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][C:26](Cl)=O)=[CH:21][CH:20]=1)[CH3:17]>ClCCl>[CH:1]1([CH2:4][N:5]2[C:6]3=[N:7][CH:8]=[C:9]([N+:13]([O-:15])=[O:14])[CH:10]=[C:11]3[N:12]=[C:26]2[CH2:25][C:22]2[CH:23]=[CH:24][C:19]([O:18][CH2:16][CH3:17])=[CH:20][CH:21]=2)[CH2:2][CH2:3]1

Participants

4

Reactant 2

HCID 116297822-(4-ethoxyphenyl)acetyl ChlorideHCID 69850017HCID 69850017, compound

Product 1

HCID 22181416HCID 22181416, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N2-(cyclopropylmethyl)-5-nitro-2,3-pyridinediamine (792 mg, 3.80 mmol) in dichloromethane (50 mL) at room temperature was added 4-ethoxy-benzeneacetyl chloride (795 mg, 4.00 mmol). The mixture was stirred for 10 hours. The mixture was concentrated in vacuo and the residue dissolved in dichloroethane (25 mL) and acetic acid (25 mL). The mixture was stirred for 48 hours at 85° C. The reaction was then cooled to room temperature and brought to pH=10 by addition of 1 M NaOH aqueous solution. The mixture was extracted with EtOAc (50 mL). The aqueous phase was back-extracted with additional EtOAc (2×50 mL). The organic phases were combined, dried with MgSO4, filtered and concentrated in vacuo. The residue was purified using silica gel flash chromatography ([2.5%. MeOH+0.5% NH4OH aq] in CH2Cl2) to provide 1.02 g of the title compound 3-(cyclopropylmethyl)-2-[(4-ethoxyphenyl)methyl]-6-nitro-3H-imidazo[4,5-b]pyridine (76.0% yield from N2-(cyclopropylmethyl)-5-nitro-2,3-pyridinediamine). 1H-NMR (400 MHz, CDCl3): δ 0.44 (m, 2H), 0.52 (m, 2H), 1.10 (m, 1H), 1.40 (t, J=6.8 Hz, 3H), 4.01 (q, J=6.8 Hz, 2H), 4.10 (d, J=7.2 Hz, 2H), 4.35 (s, 2H), 6.86 (d, J=8.8 Hz, 2H), 7.18 (d, J=8.8 Hz, 2H), 8.80 (d, J=2.3 Hz, 1H) 9.26 (d, J=2.3 Hz, 1H). MS (ESI) (M+H)+: 353.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. dissolutionthe residue dissolved in dichloroethane (25 mL)
  3. stirringThe mixture was stirred for 48 hours at 85° C
  4. additionbrought to pH=10 by addition of 1 M NaOH aqueous solution
  5. extractionThe mixture was extracted with EtOAc (50 mL)
  6. extractionThe aqueous phase was back-extracted with additional EtOAc (2×50 mL)
  7. dry with materialdried with MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified

Sources & evidence

ORD record
ord-85c3b32259e242e99dfe15f1f10bbd9e
Source dataset
uspto-grants-2006_04
Patent number
US07030139B2

Reaction notes

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