Pyridine → HCID 136397084, compound

HRID 2110608Notes

Reaction equation

HRID 2110608 reaction equation
[NH2:1][C@@:2]1([CH2:34][CH2:35][CH:36]([CH3:38])[CH3:37])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([OH:12])=[C:4]([C:13]2[NH:18][C:17]3[CH:19]=[CH:20][C:21]([NH:23]C(=O)OC(C)(C)C)=[CH:22][C:16]=3[S:15](=[O:32])(=[O:31])[N:14]=2)[C:3]1=[O:33].Cl[CH2:40][CH2:41][S:42](Cl)(=[O:44])=[O:43].C(N(CC)CC)C.[NH:53]1[CH2:58][CH2:57][O:56][CH2:55][CH2:54]1.N1C=CC=CC=1.[CH3:65][S:66](Cl)(=[O:68])=[O:67]>ClCCl>[OH:12][C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C@@:2]([NH:1][S:42]([CH2:41][CH2:40][N:53]2[CH2:58][CH2:57][O:56][CH2:55][CH2:54]2)(=[O:44])=[O:43])([CH2:34][CH2:35][CH:36]([CH3:37])[CH3:38])[C:3](=[O:33])[C:4]=1[C:13]1[NH:18][C:17]2[CH:19]=[CH:20][C:21]([NH:23][S:66]([CH3:65])(=[O:68])=[O:67])=[CH:22][C:16]=2[S:15](=[O:32])(=[O:31])[N:14]=1

Participants

8

Reactant 6

HCID 1049PyridineHCID 8083MorpholineHCID 8471Triethylamine3×HCID 15385Ethanesulfonylchloride, 2-chloro-2×HCID 31297Methanesulfonyl chlorideHCID 136396995HCID 136396995, compound

Product 1

HCID 136397084HCID 136397084, compoundYield 92.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of Example 83B (50 mg, 0.09 mmol) in dichloromethane (350 μL) at 0° C. was added 2-chloro-1-ethanesulfonyl chloride (15 μL, 0.14 mmol) and triethylamine (27 μL, 0.19 mmol) and stirring was continued at 0° C. for 1 hour. Triethylamine (19 uL, 0.14 mmol) was added and the solution was warmed to room temperature over 1 hour. 2-chloro-1-ethanesulfonyl chloride (15 μL, 0.14 mmol) and triethylamine (19 μL, 0.14 mmol) were added and stirring continued for 30 minutes. The solution was diluted with dichloromethane (5 mL) and the solution washed with brine (1×5 mL), dried (Na2SO4), the drying agent filtered off and the solvent removed in vacuo. The crude residue was dissolved in tetrahydrofuran (350 μL) and morpholine (16 μL, 0.19 mmol) was added, the solution stirred at room temperature for 16 hours and the solvent removed in vacuo. The crude residue was dissolved in 4M HCl in dioxane (4 mL) and the solution stirred at room temperature for 1 hour. Solvent was removed in vacuo and the crude residue was dissolved in dichloromethane (2 mL) and pyridine (111 μL, 1.4 mmol) and methanesulfonyl chloride (15μL, 0.19 mmol) were added and the solution stirred at room temperature for 16 hours. The sovent was removed in vacuo and the crude residue was purified by column chromatography on silica gel (2-10% methanol/chloroform) to yield the title compound as a colorless solid (58 mg, 91%); 1H NMR (d6-DMSO) δ 15.25 (s, 1H), 8.01, 7.99 (d, 1H), 7.61, 7.59 (d, 2H), 7.53-7.28 (m, 5H), 3.70-3.64 (m, 2H), 3.62-3.49 (m, 5H), 3.10-3.01 (m, 1H), 2.99 (s, 3H), 2.85-2.73 (m, 1H), 2.67-2.55 (m, 1H), 2.44-2.32 (m, 2H), 2.03-1.91 (m, 1H), 1.72-1.61 (m, 1H), 0.99-0.83 (m, 2H), 0.70-0.60 (q, 6H), 0.60-0.45 (m, 1H); MS (ESI) m/z 696 (M+H+).

Workup

  1. stirringstirring
  2. waitcontinued for 30 minutes
  3. washthe solution washed with brine (1×5 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationthe drying agent filtered off
  6. customthe solvent removed in vacuo
  7. dissolutionThe crude residue was dissolved in tetrahydrofuran (350 μL)
  8. stirringthe solution stirred at room temperature for 16 hours
  9. customthe solvent removed in vacuo
  10. dissolutionThe crude residue was dissolved in 4M HCl in dioxane (4 mL)
  11. stirringthe solution stirred at room temperature for 1 hour
  12. customSolvent was removed in vacuo
  13. dissolutionthe crude residue was dissolved in dichloromethane (2 mL)
  14. stirringthe solution stirred at room temperature for 16 hours
  15. customThe sovent was removed in vacuo
  16. customthe crude residue was purified by column chromatography on silica gel (2-10% methanol/chloroform)

Sources & evidence

ORD record
ord-2c028c610dd946229457bb28017ea518
Source dataset
uspto-grants-2009_04
Patent number
US07517876B2

Reaction notes

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