Pyridine → HCID 22272436, compound

HRID 230535Notes

Reaction equation

HRID 230535 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([S:8]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[N:18]1[CH2:24][CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20][CH2:19]1.N1C=CC=CC=1.CCN(CC)CC.[C:45]1([S:51]([Cl:54])(=[O:53])=[O:52])[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1.[OH-].[K+]>C(Cl)Cl.CCO.O>[ClH:54].[N:18]1([C:3]2[CH:4]=[CH:5][C:6]([S:8]([NH:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)(=[O:9])=[O:10])=[CH:7][C:2]=2[NH:1][S:51]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)(=[O:53])=[O:52])[CH2:24][CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1

Participants

9

Reactant 5

HCID 1049PyridineHCID 7369Benzenesulfonyl chlorideHCID 8471TriethylamineHCID 14797Potassium HydroxideHCID 22272440HCID 22272440, compound

Product 1

HCID 22272436HCID 22272436, compoundYield 48.8%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of tert-butyl 4-[2-amino-4-(anilinosulfonyl)phenyl]-1,4-diazepane-1-carboxylate (0.268 g g, 0.599 mmol), pyridine (338 μL, 4.19 mmol) and Et3N (337 μL, 2.40 mmol), in CH2Cl2 (8.0 mL) was added benzenesulfonyl chloride (153 μL, 1.20 mmol) in CH2Cl2 (2 mL). The mixture was stirred at room temperature for 16 h. The reaction mixture was washed with saturated aqueous NaHCO3, dried with Na2SO4, filtered and concentrated. The crude material was dissolved in EtOH (5 mL) and KOH (0.134 g, 4.0 equiv.) was added. The reaction was stirred at room temperature for 2 days. Water (5 mL) was added to the reaction mixture and most of the EtOH was evaporated under vacuum. The water phase was extracted with CH2Cl2 (3×20 mL). The combined organic phases were dried with Na2SO4, filtered and concentrated. The crude boc-protected material was dissolved in MeOH, and ether saturated with HCl gas was added. The mixture was stirred for 16 h and then concentrated to give 0.543 g of the crude product, which was purified by reversed phase preparative HPLC to give 0.153 g of the pure product as the acetic acid salt which was converted to the HCl-salt: 1H NMR (DMSO-d6) δ 10.25 (s, 1H), 9.09 (br s, 2H), 7.68-7.58 (m, 4H), 7.54-7.48 (m, 2H), 7.46-7.42 (m, 1H), 7.23-7.16 (m, 3H), 7.05-6.28 (m, 3H), 3.35-3.15 (m, partly obscured by solvent signal HDO, 6H), 2.81-2.75 (m, 2H), 1.92-1.85 (m, 2H);

Workup

  1. washThe reaction mixture was washed with saturated aqueous NaHCO3
  2. dry with materialdried with Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe crude material was dissolved in EtOH (5 mL)
  6. stirringThe reaction was stirred at room temperature for 2 days
  7. customwas evaporated under vacuum
  8. extractionThe water phase was extracted with CH2Cl2 (3×20 mL)
  9. dry with materialThe combined organic phases were dried with Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. dissolutionwas dissolved in MeOH
  13. additionether saturated with HCl gas was added
  14. stirringThe mixture was stirred for 16 h
  15. concentrationconcentrated
  16. customto give 0.543 g of the crude product, which
  17. customwas purified by reversed phase preparative HPLC

Sources & evidence

ORD record
ord-a0b85345674244a080bff5631fedf1a8
Source dataset
uspto-grants-2009_07
Patent number
US07566715B2

Reaction notes

Loading…