Water → HCID 68943639, compound

HRID 2189366Notes

Reaction equation

HRID 2189366 reaction equation
Cl[S:2]([N:5]=C=O)(=[O:4])=[O:3].O.[C:9]([O:12][C@@H:13]1[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@H:17]([O:23][C:24](=[O:26])[CH3:25])[C@@H:16]([CH2:27][O:28][C:29](=[O:31])[CH3:30])[O:15][C@H:14]1[O:32][C:33]1[C:37]([CH2:38][C:39]2[CH:44]=[CH:43][C:42]([O:45][CH2:46][CH2:47][CH2:48][NH2:49])=[CH:41][CH:40]=2)=[C:36]([CH:50]([CH3:52])[CH3:51])[NH:35][N:34]=1)(=[O:11])[CH3:10].C(N(CC)CC)C>C(#N)C.ClCCl>[C:9]([O:12][C@@H:13]1[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@H:17]([O:23][C:24](=[O:26])[CH3:25])[C@@H:16]([CH2:27][O:28][C:29](=[O:31])[CH3:30])[O:15][C@H:14]1[O:32][C:33]1[C:37]([CH2:38][C:39]2[CH:44]=[CH:43][C:42]([O:45][CH2:46][CH2:47][CH2:48][NH:49][S:2](=[O:4])(=[O:3])[NH2:5])=[CH:41][CH:40]=2)=[C:36]([CH:50]([CH3:52])[CH3:51])[NH:35][N:34]=1)(=[O:11])[CH3:10]

Participants

7

Reactant 4

HCID 962Water2×HCID 8471TriethylamineHCID 70918Chlorosulfonyl isocyanateHCID 68937787HCID 68937787, compound

Product 1

HCID 68943639HCID 68943639, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of chlorosulfonyl isocyanate (0.022 mL) in acetonitrile (1 mL) was added water (0.005 mL), and the mixture was stirred at room temperature for 10 minutes. This reaction mixture was added to a solution of 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-{[4-(3-aminopropoxy)phenyl]-methyl}-5-isopropyl-1H-pyrazole (51 mg) and triethylamine (0.052 mL) in dichloromethane (2 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: dichloromethane/methanol=30/1) to give 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-5-isopropyl-4-({4-[3-(sulfamoylamino)propoxy]phenyl)methyl}-1H-pyrazole (18 mg). This material was dissolved in methanol (2 mL). To the solution was added sodium methoxide (28% methanol solution, 0.01 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue was purified by solid phase extraction on ODS (washing solvent: distilled water, eluent: methanol) to give the title compound (3 mg).

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. extractionthe resulting mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was removed under reduced pressure
  6. customthe residue was purified by column chromatography on silica gel (eluent: dichloromethane/methanol=30/1)

Sources & evidence

ORD record
ord-ca71796f278f4de2b09be1f6688d06f3
Source dataset
uspto-grants-2012_12
Patent number
US08324176B2

Reaction notes

Loading…