Hydroxylamine → HCID 22890444, compound

HRID 993135Notes

Reaction equation

HRID 993135 reaction equation
C([O:3][C:4](=[O:42])[CH2:5][S:6](=[O:41])(=[O:40])[NH:7][C:8]1[CH:13]=[C:12]([O:14][CH2:15][CH3:16])[C:11]([O:17][CH2:18][CH3:19])=[CH:10][C:9]=1[C@@H:20]1[CH2:24][N:23]([S:25]([CH2:28][CH2:29][CH3:30])(=[O:27])=[O:26])C(=O)[N:21]1[C:32]1[CH:37]=[CH:36][C:35]([C:38]#[N:39])=[CH:34][CH:33]=1)C.[OH-].[Li+].NO.CC[N:49](C(C)C)C(C)C>C(O)C.[Ni].C(O)(=O)C>[C:38]([C:35]1[CH:36]=[CH:37][C:32]([NH:21][CH:20]([C:9]2[CH:10]=[C:11]([O:17][CH2:18][CH3:19])[C:12]([O:14][CH2:15][CH3:16])=[CH:13][C:8]=2[NH:7][S:6]([CH2:5][C:4]([OH:3])=[O:42])(=[O:40])=[O:41])[CH2:24][NH:23][S:25]([CH2:28][CH2:29][CH3:30])(=[O:27])=[O:26])=[CH:33][CH:34]=1)(=[NH:39])[NH2:49]

Participants

8

Reactant 4

HCID 787HydroxylamineHCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 54473070HCID 54473070, compound

Product 1

HCID 22890444HCID 22890444, compound

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 176Acetic AcidSolventHCID 702EthanolSolvent3×

Conditions

Temperature
60 °C

Procedure

(R)-{2-[3-(4-cyanophenyl)-2-oxo-1-(propane-1-sulfonyl)-imidazolidin-4-yl]-4,5-diethoxyphenylsulfamoyl}-acetic acid ethyl ester (0.160 g) was diluted with ethanol (5 mL) followed by lithium hydroxide (1 mL of a 10% aqueous solution, 10 Equiv.) and the solution was stirred for forty eight hours. The solution was purified by direct flash chromatography on silica gel (20% methanol/80% dichloromethane) to yield the product. This product was diluted with ethanol (1 mL) and hydroxylamine (0.035 g, 10 Equiv.) and Hunigs base (0.088 mL, 10 Equiv.) was added and the solution was heated to 60° C. for six hours. The reaction mixture was cooled to room temperature and stirred for twelve hours. Ethanol (3 mL) and acetic acid (0.5 mL), and Raney nickel (0.025 g) was added and the solution was hydrogenated for one hour. The reaction mixture was filtered through a pad of celite and the solvent was removed under reduced pressure. The product was purified by reverse-phase preparative chromatography to yield {2-[1-(4-carbamimidoylphenylamino)-2-(propane-1-sulfonylamino)-ethyl]-4,5-diethoxyphenylsulfamoyl} acetic acid (52 mg). [α]Na −42.1 (c 1.01, methanol) MS (M+H)=587.

Workup

  1. customThe solution was purified by direct flash chromatography on silica gel (20% methanol/80% dichloromethane)
  2. customto yield the product
  3. additionwas added
  4. temperatureThe reaction mixture was cooled to room temperature
  5. stirringstirred for twelve hours
  6. filtrationThe reaction mixture was filtered through a pad of celite
  7. customthe solvent was removed under reduced pressure
  8. customThe product was purified by reverse-phase preparative chromatography

Sources & evidence

ORD record
ord-ebeb3a5a5e7c473f9877977a94401c12
Source dataset
uspto-grants-2002_10
Patent number
US06472393B1

Reaction notes

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