Phosphorus oxychloride → HCID 66744626, compound

HRID 1959345Notes

Reaction equation

HRID 1959345 reaction equation
[NH2:1][C:2]1[C:3]([C:19]([NH:21][NH:22][C:23](=[O:30])[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=O)=[N:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([S:14]([CH2:17][CH3:18])(=[O:16])=[O:15])[CH2:10][CH2:9]2)=[CH:6][N:7]=1.P(Cl)(Cl)(Cl)=O>>[CH2:17]([S:14]([N:11]1[CH2:12][CH2:13][N:8]([C:5]2[N:4]=[C:3]([C:19]3[O:30][C:23]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[N:22][N:21]=3)[C:2]([NH2:1])=[N:7][CH:6]=2)[CH2:9][CH2:10]1)(=[O:16])=[O:15])[CH3:18]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 667457353-amino-N'-benzoyl-6-(4-ethylsulfonylpiperazin-1-yl)pyrazine-2-carbohydrazide

Product 1

HCID 66744626HCID 66744626, compoundYield 101.9%

Conditions

Temperature
100 °C

Procedure

A mixture of 3-amino-N′-benzoyl-6-(4-ethylsulfonylpiperazin-1-yl)pyrazine-2-carbohydrazide (50 mg, 0.1153 mmol) in phosphorus oxychloride (884.0 mg, 537.4 μL, 5.765 mmol) was heated at 100° C. for 3 hours. The mixture was allowed to cool to RT and added carefully to ice water. The mixture was extracted with EtOAc (3×10 mL) and the combined organics washed with 1N NaOH and brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 uM, 100A column, gradient 10%-95% B (solvent A: 0.05% TFA in water, solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected and freeze-dried to give the title compound (48.8 mg, 80% Yield). 1H NMR (400.0 MHz, DMSO) d 1.24 (3H, t), 3.11 (2H, q), 3.33-3.36 (4H, m), 3.56 (4H, masked signal), 6.95 (2H, br s), 7.63-7.69 (3H, m), 8.11-8.13 (2H, m), 8.28 (1H, s) ppm; MS (ES+) 416.01

Workup

  1. temperatureto cool to RT
  2. extractionThe mixture was extracted with EtOAc (3×10 mL)
  3. washthe combined organics washed with 1N NaOH and brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe resultant residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 uM, 100A column, gradient 10%-95% B (solvent A: 0.05% TFA in water, solvent B: CH3CN) over 16 minutes at 25 mL/min]
  7. customThe fractions were collected
  8. customfreeze-dried

Sources & evidence

ORD record
ord-cfc6475899ae429f861cc707c7a45f77
Source dataset
uspto-grants-2013_04
Patent number
US08410112B2

Reaction notes

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