Hydrochloric Acid → HCID 68323736, compound

HRID 573614Notes

Reaction equation

HRID 573614 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([S:8]([NH:11][C:12]2[CH:17]=[C:16]([CH3:18])[N:15]=[C:14]3[S:19][C:20]([CH3:41])=[C:21]([C:22]4[CH:23]=[C:24]([N:28]5[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30][CH2:29]5)[CH:25]=[CH:26][CH:27]=4)[C:13]=23)(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.Cl.O1CCOCC1.[OH-].[Na+]>C(Cl)Cl.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([S:8]([NH:11][C:12]2[CH:17]=[C:16]([CH3:18])[N:15]=[C:14]3[S:19][C:20]([CH3:41])=[C:21]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([N:28]5[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]5)[CH:23]=4)[C:13]=23)(=[O:9])=[O:10])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 14798Sodium HydroxideHCID 312751,4-Dioxane2×HCID 68323817HCID 68323817, compound

Product 1

HCID 68323736HCID 68323736, compoundYield 25.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1,1-dimethylethyl 4-[3-(4-{[(3-chlorophenyl)sulfonyl]amino}-2,6-dimethylthieno[2,3-b]pyridin-3-yl)phenyl]-1-piperazinecarboxylate (60 mg, 0.098 mmol) (Example 31) in DCM (2 mL) was added 4M HCl in dioxane (0.122 mL, 0.489 mmol) and the mixture stirred for 3 h. Additional 4M HCl in dioxane (2.446 mL, 9.78 mmol) was then added and the mixture stirred overnight. Aqueous NaOH (5M) was then added to the solution dropwise until it was basic. Ethyl acetate (10 mL) was added and the mixture washed with water (2×5 mL). The organic layer was dried over MgSO4, filtered and the solvent removed in vacuo. The residue was purified by MDAP (acidic conditions) and further purification using HPLC (CHIRALPAK AD (250×20 mm-10 micron); isohexane/ethanol gradient, 18 mL/min) afforded the title compound (12.7 mg). LCMS (A) m/z: 513 [M+1]+, Rt 0.93 min (basic), Rt 1.01 min (acidic).

Workup

  1. stirringthe mixture stirred overnight
  2. washthe mixture washed with water (2×5 mL)
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. customthe solvent removed in vacuo
  6. customThe residue was purified by MDAP (acidic conditions) and further purification

Sources & evidence

ORD record
ord-9aa3416f709943dfb10b0df3bca56817
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

Loading…