Hydrochloric Acid → HCID 66745468, compound

HRID 1959405Notes

Reaction equation

HRID 1959405 reaction equation
C(N(CC)CC)C.C(OC([N:15]([C:23]1[C:28]([C:29]#[CH:30])=[N:27][C:26]([N:31]2[CH2:36][CH2:35][N:34]([S:37]([CH2:40][CH3:41])(=[O:39])=[O:38])[CH2:33][CH2:32]2)=[CH:25][N:24]=1)C(=O)OC(C)(C)C)=O)(C)(C)C.[OH:42][N:43]=[C:44](Cl)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1.Cl.O1CCOCC1>C1COCC1>[CH2:40]([S:37]([N:34]1[CH2:35][CH2:36][N:31]([C:26]2[N:27]=[C:28]([C:29]3[O:42][N:43]=[C:44]([C:45]4[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=4)[CH:30]=3)[C:23]([NH2:15])=[N:24][CH:25]=2)[CH2:32][CH2:33]1)(=[O:38])=[O:39])[CH3:41]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 2756315N-hydroxybenzenecarboximidoyl chlorideHCID 86662075HCID 86662075, compound

Product 1

HCID 66745468HCID 66745468, compoundYield 23.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (10.21 mg, 14.06 μL, 0.1009 mmol) was added to a solution of tert-butyl N-tert-butoxycarbonyl-N-[5-(4-ethylsulfonylpiperazin-1-yl)-3-ethynyl-pyrazin-2-yl]carbamate (50 mg, 0.1009 mmol) and N-hydroxybenzimidoyl chloride (15.70 mg, 0.1009 mmol) in THF (4 mL) and the reaction mixture allowed to stir at ambient temperature for 1 hour. After this time the reaction mixture was heated under reflux for 3 hours and allowed to cool to RT. The reaction was treated with HCl in dioxane (126.1 μL of 4 M, 0.5045 mmol), allowed to stir overnight at ambient temperature, concentrated in vacuo and 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 an orange solid (9.9 mg, 18% Yield). 1H NMR (DMSO) d 1.03 (3H, t), 2.90 (2H, q), 3.11 (4H, m), 3.33 (4H, m), 5.88 (2H, br s), 7.34-7.36 (4H, m), 7.77 (2H, m), 7.92 (1H, s) ppm; MS (ES+) 414.98

Workup

  1. temperatureAfter this time the reaction mixture was heated
  2. temperatureunder reflux for 3 hours
  3. temperatureto cool to RT
  4. stirringto stir overnight at ambient temperature
  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-bb4b7349d03b47279918a9b818ed9800
Source dataset
uspto-grants-2013_04
Patent number
US08410112B2

Reaction notes

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