1,1'-Carbonyldiimidazole → HCID 46199245, compound

HRID 1959344Notes

Reaction equation

HRID 1959344 reaction equation
[CH2:1]([S:3]([N:6]1[CH2:11][CH2:10][N:9]([C:12]2[N:13]=[C:14]([C:19]3[O:20]C(C4C=CC=CC=4)=N[N:23]=3)[C:15]([NH2:18])=[N:16][CH:17]=2)[CH2:8][CH2:7]1)(=[O:5])=[O:4])[CH3:2].C1N=CN(C(N2C=NC=C2)=O)C=1.NC1C(C(O)=O)=NC(N2CCN(S(CC)(=O)=O)CC2)=CN=1.O[N:64]=[C:65](N)[C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1>CN(C=O)C.O>[CH2:1]([S:3]([N:6]1[CH2:11][CH2:10][N:9]([C:12]2[N:13]=[C:14]([C:19]3[O:20][N:64]=[C:65]([C:66]4[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=4)[N:23]=3)[C:15]([NH2:18])=[N:16][CH:17]=2)[CH2:8][CH2:7]1)(=[O:5])=[O:4])[CH3:2]

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 69186N'-HydroxybenzenecarboximidamideHCID 667445273-Amino-6-(4-(ethylsulfonyl)piperazin-1-yl)pyrazine-2-carboxylic acidHCID 66744626HCID 66744626, compound

Product 1

HCID 46199245HCID 46199245, compoundYield 30%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

5-(4-(ethylsulfonyl)piperazin-1-yl)-3-(5-phenyl-1,3,4-oxadiazol-2-yl)pyrazin-2-amine (Compound I-19) CDI (102.8 mg, 0.6342 mmol) was added to a solution of 3-amino-6-(4-ethylsulfonylpiperazin-1-yl)pyrazine-2-carboxylic acid (100 mg, 0.3171 mmol) and N′-hydroxybenzamidine (86.35 mg, 0.6342 mmol) in DMF (3.000 mL) and the resulting solution stirred at RT for 3 hours and then heated at 100° C. overnight. The mixture was allowed to cool, poured in water and extracted with EtOAc. The organic extract was washed with water (2×), brine, dried over Na2SO4, filtered 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 as a bright yellow solid (53.6 mg, 30% Yield). 1H NMR (400.0 MHz, DMSO) d 1.24 (3H, t), 3.11 (2H, q), 3.33 (4H, m), 3.55 (4H, m), 7.18 (2H, br s), 7.59-7.66 (3H, m), 8.19 (2H, m), 8.42 (1H, s) ppm; MS (ES+) 416

Workup

  1. temperatureheated at 100° C. overnight
  2. temperatureto cool
  3. extractionextracted with EtOAc
  4. extractionThe organic extract
  5. washwas washed with water (2×), brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. 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]
  10. customThe fractions were collected
  11. customfreeze-dried

Sources & evidence

ORD record
ord-86f7898be3e547c1b53d5407984b6747
Source dataset
uspto-grants-2013_04
Patent number
US08410112B2

Reaction notes

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