Pyridine → Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-methanesulfonylamino-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

HRID 2353879Notes

Reaction equation

HRID 2353879 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[CH:6]([O:9][C:10]([N:12]1[CH2:18][CH2:17][CH2:16][CH:15]([N:19]([C:35](=[O:37])[CH3:36])[CH2:20][C:21]2[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:22]=2)[C:14]2[CH:38]=[CH:39][C:40]([NH2:42])=[CH:41][C:13]1=2)=[O:11])([CH3:8])[CH3:7].N1C=CC=CC=1>ClCCl>[C:35]([N:19]([CH2:20][C:21]1[CH:22]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:24]=[C:25]([C:27]([F:30])([F:28])[F:29])[CH:26]=1)[CH:15]1[CH2:16][CH2:17][CH2:18][N:12]([C:10]([O:9][CH:6]([CH3:8])[CH3:7])=[O:11])[C:13]2[CH:41]=[C:40]([NH:42][S:2]([CH3:1])(=[O:4])=[O:3])[CH:39]=[CH:38][C:14]1=2)(=[O:37])[CH3:36]

Participants

5

Reactant 3

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 59003104Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-amino-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

Product 1

HCID 59003125Isopropyl 5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-methanesulfonylamino-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylateYield 58.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add methanesulfonyl chloride (13 μl, 0.170 mmol) dropwise to a suspension of isopropyl-5-[acetyl-(3,5-bistrifluoromethylbenzyl)amino]-8-amino-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate (0.082 g, 0.154 mmol) and pyridine (15 μl, 0.185 mmol) in dichloromethane (2 mL) at 0° C. under nitrogen. Stir the orange suspension for 0.5 h, then remove the cooling bath and warm the mixture to room temperature and stir overnight. Dilute the mixture with dichloromethane (30 mL) and wash with 2 N HCl, water and brine (10 mL each), then dry the organic layer over sodium sulfate, filter and remove the solvent under reduced pressure. Purify the residue using chromatography on silica gel, eluting with ethyl acetate/hexanes (70:30), to provide the title compound as a white solid (0.055 g, 58%): ESI MS 610 (M+H).

Workup

  1. customremove the cooling bath
  2. stirringstir overnight
  3. additionDilute the mixture with dichloromethane (30 mL)
  4. washwash with 2 N HCl, water and brine (10 mL each)
  5. dry with materialdry the organic layer over sodium sulfate
  6. filtrationfilter
  7. customremove the solvent under reduced pressure
  8. customPurify the residue
  9. washeluting with ethyl acetate/hexanes (70:30)

Sources & evidence

ORD record
ord-5870b0f5078f47ff905fa472d9099a6a
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

Loading…