Pyridine → HCID 22272502, compound

HRID 1064511Notes

Reaction equation

HRID 1064511 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:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:20][CH2:19]1.[CH3:32][S:33](Cl)(=[O:35])=[O:34].N1C=CC=CC=1>>[NH:11]([S:8]([C:6]1[CH:5]=[CH:4][C:3]([N:18]2[CH2:24][CH2:23][CH2:22][N:21]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:20][CH2:19]2)=[C:2]([NH:1][S:33]([CH3:32])(=[O:35])=[O:34])[CH:7]=1)(=[O:9])=[O:10])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

4

Reactant 3

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 22272440HCID 22272440, compound

Product 1

HCID 22272502HCID 22272502, compoundYield 58%

Procedure

A mixture of tert-butyl 4-[2-amino-4-(anilinosulfonyl)phenyl]-1,4-diazepane-1-carboxylate (176 mg, 0.39 mmol), methylsulfonyl chloride (0.040 mL, 0.47 mmol) and pyridine (0.285 mL, 3.51 mmol) in CH2CL2 (5 mL) was stirred at room temperature overnight. The reaction mixture was quenched with NaHCO3 aq (3×30 mL). The organic phase was separated, dried (MgSO4) and filtered. The volatiles were evaporated followed by purification of the oily residue by chromatography (SiO2, hexane/EtOAc 4:1) to give 110 mg of tert-butyl 4-{4-(anilinosulfonyl)-2-[(methylsulfonyl)amino]phenyl}-1,4-diazepane-1-carboxylate (yield 58%). 1H NMR (CDCl3) δ 7.90-7.85 (m, 1H), 7.50-7.43 (m, 1H), 7.30-7.24 (m, 2H), 7.20-7.08 (m, 4H), 6.84-6.79 (m, 1H), 3.65-3.51 (m, 4H), 3.12-3.06 (m, 1H), 3.04-2.96 (m, 6H), 2.04-1.91 (m, 2H), 1.49 (s, 3H); MS (posEI-DIP) m/z=524 (M+H+). tert-Butyl 4-{4-(anilinosulfonyl)-2-[(methylsulfonyl)amino]phenyl}-1,4-diazepane-1-carboxylate (0.077 g, 0.147 mmol) was dissolved in MeOH, and ether saturated with HCl gas was added. The mixture was stirred at room temperature for 4 h and then concentrated. The crude solid was dissolved in a small amount of MeOH, and ether was added. The precipitate was collected and dried to give 30 mg of the pure product as the HCl salt (yield 48%): 1H NMR (DMSO-d6) δ 7.72-7.70 (m, 1H), 7.46-7.42 (m, 1H), 7.25-7.20 (m, 3H), 7.14-7.09 (m, 2H), 7.03-6.99 (m, 1H), 3.45-3.15 (m, partly obscured by solvent signal, HDO, 6H), 2.96 (s, 3H), 2.02-1.95 (m, 2H); MS (posES-FIA) m/z=425 (M+H+).

Workup

  1. customThe reaction mixture was quenched with NaHCO3 aq (3×30 mL)
  2. customThe organic phase was separated
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customThe volatiles were evaporated
  6. customfollowed by purification of the oily residue by chromatography (SiO2, hexane/EtOAc 4:1)

Sources & evidence

ORD record
ord-3e1a5e0dd514408d9169e6ce0f8fe7f4
Source dataset
uspto-grants-2005_11
Patent number
US06969710B2

Reaction notes

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