Chloroacetyl chloride → HCID 59853068, compound

HRID 2374009Notes

Reaction equation

HRID 2374009 reaction equation
[F:1][C:2]1[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[CH:15][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[CH:7][C:6]=1[C:11]#[C:12][CH2:13][NH2:14].Cl[CH2:23][C:24](Cl)=[O:25].[NH:27]1[CH2:31][CH2:30][CH2:29][C:28]1=O>C(Cl)Cl>[F:1][C:2]1[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[CH:15][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[CH:7][C:6]=1[C:11]#[C:12][CH2:13][NH:14][C:24](=[O:25])[CH2:23][N:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1

Participants

5

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 120252-PyrrolidoneHCID 598529072-Propyn-1-amine, 3-[4-(2-fluoro-4-nitrophenoxy)-3-pyridinyl]-

Product 1

HCID 59853068HCID 59853068, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 3-(4-(2-fluoro-4-nitrophenoxy)pyridin-3-yl)prop-2-yn-1-amine (80 mg, 0.26 mmol) in anhydrous CH2Cl2 (2.5 mL) was cooled to 0° C. and treated with chloroacetyl chloride (40 mg, 0.37 mmol) the mixture was stirred at rt for 1 h. The mixture was concentrated under vacuum to removed the solvent and excess reagent and the residue redissolved in CH3CN (1.5 mL), treated with pyrrolidone (55 mg, 0.78 mmol) and stirred at rt for 4 h. The mixture was partitioned between EtOAc and saturated aq. NaHCO3 solution and the organic phase separated, washed with brine, dried (MgSO4) and concentrated to give crude product. The residue was purified by flash chromatography on silica gel eluting with 0-10% MeOH/CH2Cl2 to afford the title compound (40 mg, 39%) as a brown oil. 1H NMR (DMSO-d6) δ 8.66 (s, 1H), 8.50 (d, 1H, J=6.1 Hz), 8.41 (dd, 1H, J=2.8, 10.4 Hz), 8.18-8.15 (m, 2H), 7.51 (dd, 1H, J=8.3, 8.8 Hz), 7.06 (d, 1H, J=5.5 Hz) 4.10 (d, 2H, J=5.5 Hz), 3.01 (s, 2H), 2.47-2.43 (m, 4H), 1.67-1.63 (m, 4H); MS(ESI+): m/z 399.27 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated under vacuum
  2. customto removed the solvent and excess reagent
  3. dissolutionthe residue redissolved in CH3CN (1.5 mL)
  4. stirringstirred at rt for 4 h
  5. customThe mixture was partitioned between EtOAc and saturated aq. NaHCO3 solution
  6. customthe organic phase separated
  7. washwashed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customto give crude product
  11. customThe residue was purified by flash chromatography on silica gel eluting with 0-10% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-051d4c44d19541c38350a970ceb26984
Source dataset
uspto-grants-2008_12
Patent number
US07459562B2

Reaction notes

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