Hydrochloric Acid → HCID 66745250, compound

HRID 1959404Notes

Reaction equation

HRID 1959404 reaction equation
[CH2:1]([S:3](Cl)(=[O:5])=[O:4])[CH3:2].C(OC([N:14](C(OC(C)(C)C)=O)[C:15]1[C:16]([C:27]2[N:28](C(OC(C)(C)C)=O)[C:29]3[C:34]([CH:35]=2)=[CH:33][CH:32]=[CH:31][CH:30]=3)=[N:17][C:18]([N:21]2[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)=[CH:19][N:20]=1)=O)(C)(C)C.C(N(CC)CC)C.Cl.O1CCOCC1>C(Cl)Cl>[CH2:1]([S:3]([N:24]1[CH2:23][CH2:22][N:21]([C:18]2[N:17]=[C:16]([C:27]3[NH:28][C:29]4[C:34]([CH:35]=3)=[CH:33][CH:32]=[CH:31][CH:30]=4)[C:15]([NH2:14])=[N:20][CH:19]=2)[CH2:26][CH2:25]1)(=[O:5])=[O:4])[CH3:2]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 11667Ethanesulfonyl chlorideHCID 312751,4-DioxaneHCID 66745112HCID 66745112, compound

Product 1

HCID 66745250HCID 66745250, compoundYield 8.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Ethanesulfonyl chloride (43.25 mg, 31.87 μL, 0.3364 mmol) was added to a solution of tert-butyl 2-[3-(bis(tert-butoxycarbonyl)amino)-6-piperazin-1-yl-pyrazin-2-yl]indole-1-carboxylate (100 mg, 0.1682 mmol) and triethylamine (18.72 mg, 25.79 μL, 0.1850 mmol) in DCM (2 mL) at 0° C. and the reaction mixture allowed to stir at ambient temperature for 30 minutes. The reaction was then treated with HCl in dioxane (210.2 μL of 4 M, 0.8410 mmol) and allowed to stir at ambient temperature overnight. The mixture was 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, passed through a sodium bicarbonate cartridge and freeze-dried to give the title compound as a yellow solid (5.5 mg, 8% Yield). 1H NMR (DMSO) d 1.25 (3H, t), 3.12 (2H, q), 3.30 masked signal, 3.59 (4H, m), 5.66 (2H, br s), 7.00-7.04 (1H, m), 7.14-7.18 (2H, m), 7.51 (1H, m), 7.58 (1H, m), 7.81 (1H, s), 11.25 (1H, br s) ppm; MS (ES+) 386.87

Workup

  1. stirringto stir at ambient temperature overnight
  2. concentrationThe mixture was concentrated in vacuo
  3. 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]
  4. customThe fractions were collected
  5. customfreeze-dried

Sources & evidence

ORD record
ord-887cd99ce79a44f29324576b94e4d011
Source dataset
uspto-grants-2013_04
Patent number
US08410112B2

Reaction notes

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