| Identification | Back Directory | [Name]
1-[(2R)-4-[5-[(4-fluorophenyl)methyl]thiophen-2-yl]but-3-yn-2-yl]-1-hydroxy-urea | [CAS]
154355-76-7 | [Synonyms]
A8576
VIA-2291
Atreleuton-d4
Atreleuton >=98% (HPLC)
1-[(2R)-4-[5-[(4-fluorophenyl)methyl]thiophen-2-yl]but-3-yn-2-yl]-1-hydroxy-urea
(R)-N-(3-(5-(4-Fluorophenylmethyl)thien-2-yl)-1-methyl-2-propynyl)-N-hydroxyurea
Urea, N-[(1R)-3-[5-[(4-fluorophenyl)methyl]-2-thienyl]-1-methyl-2-propyn-1-yl]-N-hydroxy- | [Molecular Formula]
C16H15FN2O2S | [MDL Number]
MFCD00928115 | [MOL File]
154355-76-7.mol | [Molecular Weight]
318.37 |
| Chemical Properties | Back Directory | [storage temp. ]
2-8°C | [solubility ]
DMSO: soluble10mg/mL, clear | [form ]
powder | [color ]
white to beige | [optical activity]
[α]/D +40 to +50°, c = 1 in methanol |
| Hazard Information | Back Directory | [Originator]
Abbott-85761,Abbott | [Uses]
Anti-asthmatic;
inhibitor (5-lipoxygenase). | [Manufacturing Process]
A solution of thiophene (12.6 g, 0.15 mol) in a mixture of anhydrous ether
(230 ml) and anhydrous THF (70 ml) was treated dropwise at 0°C with a 2.5
M solution of n-butyl lithium in hexane (54.0 ml, 0.134 mol). The mixture was
stirred at 0°C for 1.5 h and then transferred by cannula into a -78°C solution
of 4-fluorobenzylbromide (23.6 g, 0.125 mol) containing
tetrakis(triphenylphosphine)palladium(O) (1.25 g) in anhydrous THF (200 ml).
The reaction mixture was stirred for 17 h at room temperature and then
quenched with saturated aqueous NH4Cl solution (100 ml) and partitioned
between ether and additional NH4Cl solution. The ether layer was dried over
MgSO4, concentrated in vacuum and the residue subjected to vacuum
distillation to give 19.4 g (81%) of 2-(4-fluorophenylmethyl)thiophene, boiling
point 74°-83°C at 0.6-0.7 mm of Hg.
A mixture of 2-(4-fluorophenylmethyl)thiophene (3.85 g, 20.0 mmol) and Niodosuccinimide
(4.50 g, 20.0 mmol) in 1:1 chloroform-acetic acid (40 ml)
was stirred at room temperature for 1 h and then diluted with an equal
volume of water. The organic layer was washed with saturated aqueous
NaHCO3 solution (2 times 50 ml), 10% aqueous sodium thiosulfate solution (2
times 50 ml) and once with brine. After drying over MgSO4, the organic layer
was concentrated in vacuum to give 6.07 g (95%) of 2-iodo-5-(4-
fluorophenylmethyl)thiophene as a gold colored oil.
To a solution of (S)-O-p-toluenesulfonyl-3-butyn-2-ol (11.2 g, 50.0 mmol),
prepared by addition of p-toluenesulfonyl chloride and triethylamine to (S)-3-
butyn-2-ol, in methanol (100 ml), was added 55% aqueous hydroxylamine
(30 ml, 0.50 mol) and the reaction mixture was stirred at room temperature
for 40 h. The reaction mixture was cooled to 10°C and concentrated HCl (50
ml) was added dropwise. The reaction mixture was concentrated in vacuum
and the residue was partitioned between H2O (50 ml) and ethyl acetate (200
ml). The 2-phase mixture was cooled to 10°C and taken to pH 8 with 50%
aqueous NaOH solution (60 ml). After stirring for 15 min the layers were
separated and the aqueous phase was extracted twice with 200 ml of ethyl
acetate. The combined ethyl acetate extracts were cooled to 10°C and a
solution of KOCN (8.1 g, 0.10 mmol) in H2O (30 ml) was added, followed by
dropwise addition of 11 ml of concentrated HCl, and the reaction mixture was stirred for 30 min. The ethyl acetate layer was separated and the aqueous
layer was extracted twice with ethyl acetate. The combined organic layers
were dried over MgSO4, filtered, and concentrated in vacuum to give 5.9 g
(92% yield) of (R)-N-hydroxy-N-(3-butyn-2-yl)urea, melting point 129°C.
To a solution of 2-iodo-5-(4-fluorophenylmethyl)thiophene (5.30 g, 16.6
mmol), in anhydrous DMF (5.0 ml) was added (R)-N-hydroxy-N-(3-butyn-2-
yl)urea (2.12 g, 16.6 mmol), triphenylphosphine (84.0 mg, 0.32 mmol),
bis(acetonitrile)palladium(II) chloride (40.0 mg, 0.16 mmol), copper(I) iodide
(16.0 mg, 0.08 mmol), and diethylamine (5.6 ml). The mixture was stirred
under nitrogen at room temperature for 22 h and concentrated in vacuum at
32°C. The residue was subjected to chromatography on silica eluting with 2-
7% MeOH in CH2Cl2, crystallization from ethyl acetate-hexane and trituration
in CH2Cl2 to afford (R)-N-{3-[5-(4-fluorophenylmethyl)thien-2-yl]-1-methyl-2-
propynyl}-N-hydroxyurea as a cream-colored solid 0.94 g (18%), melting
point 135°-136°C, (dec). | [Therapeutic Function]
Antiallergic, Anti-asthmatic | [storage]
Store at -20°C |
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