Triethylamine → HCID 86629772, compound

HRID 2387185Notes

Reaction equation

HRID 2387185 reaction equation
C(N(CC)CC)C.CN(C)S([N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)(=O)=O.Cl[C:21]1[N:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][N:22]=1>C1COCC1>[N+:27]([C:24]1[CH:23]=[N:22][C:21]([CH:15]2[CH2:14][NH:13][CH2:18][CH2:17][NH:16]2)=[N:26][CH:25]=1)([O-:29])=[O:28]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 825442-Chloro-5-nitropyrimidineHCID 1094966N,N-dimethylpiperazine-1-sulfonamide

Product 1

HCID 86629772HCID 86629772, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Triethylamine (7.2 mL, 51.8 mmol) was added to a solution of piperazine-1-sulfonic acid dimethyl amide (10 g, 51.8 mmol) dissolved in 400 mL of THF. 2-chloro-5-nitropyrimidine (7.7 g, 48.3 mmol) dissolved in 20 mL of THF was added to the stirred mixture. After 24 hours stirring at room temperature (RT), THF was removed under vacuum and 600 mL of CHCl3 was added to the residue. The CHCl3 layer was washed with 0.5 N HCl and brine, dried over Na2SO4, and filtered. Solvent evaporation gave 14.1 g (92%) of straw yellow solid 1-N,N′-dimethylsulfamoyl-4-(2-(5-nitropyrimidyl)piperazine. The structure was confirmed by 1H-NMR. 1H NMR (CDCl3) δ9.08 (s, 2H), 4.09 (appt, J=5.13 Hz, 4H), 3.35 (appt, J=5.13 Hz, 4H), 2.87 (s, 6H). Step 2: NH4Cl (1.43 g, 26.76 mmol) was added to a suspension of 1-N,N′-dimethylsulfamoyl-4-(2-(5-nitropyrimidyl)piperazine (14.1 g, 44.6 mmol) in a mixture of EtOH (175 mL) and H2O (48 mL), followed by iron powder (7.5 g, 133.9 mmol). After refluxing 1 hour, the reaction mixture was filtered and concentrated to give a brown solid which was dissolved in 800 mL of CHCl3, washed with NaHCO3 and brine, dried over Na2SO4, and filtered. Solvent evaporation gave a yellow solid which after CC with 100:1 CHCl3:MeOH gave 11.5 g (90%) of solid yellow 1-N,N′-dimethylsulfamoyl-4-(2-(5-nitro-pyrimidyl)-piperazine. The structure was confirmed by 1H-NMR and EI-MS. 1H NMR (CDCl3) δ7.98 (s, 2H), 3.76 (t, J=4.88 Hz, 4H), 3.30 (t, J=4.88 Hz, 4H), 2.86 (s, 6H); EI-MS (m/z) 286 (M+). Step 3: A suspension of 1-N,N′-dimethylsulfamoyl-4-(2-(5-nitro-pyrimidyl)-piperazine (5.76 g, 20.2 mmol) in 100 mL of 2 M H2SO4 was refluxed for 1.5 hours until the suspension became clear. After cooling to RT, the solution pH was adjusted to 6-7 with 10 N NaOH, and the cloudy mixture was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, and filtered. Solvent evaporation gave a yellow solid, which was purified by CC using 1:1 EtOAc:hexane to yield 3.23 g (56%) of white solid JHX-2, mp 134-135° C. The structure was confirmed by 1H-NMR, 13C-NMR, ESI-MS and elemental analysis. 1H NMR (CDCl3) δ8.08 (s, 2H), 3.78 (appt, J=5.13 Hz, 4H), 3.29 (appt, J=5.13 Hz, 4H), 2.86 (s, 6H); 13C NMR (CDCl3) 156.9, 145.8, 143.5, 46.0, 44.3, 38.1; EI-MS (m/z) 287 (M+).

Workup

  1. additionwas added to the stirred mixture
  2. customwas removed under vacuum and 600 mL of CHCl3
  3. additionwas added to the residue
  4. washThe CHCl3 layer was washed with 0.5 N HCl and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customSolvent evaporation

Sources & evidence

ORD record
ord-e8e6ff2f1eed410dbd98223010bfc2f5
Source dataset
uspto-grants-2012_09
Patent number
US08268849B2

Reaction notes

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