(+)-Terconazole

Example 17 : (2R,4S)-(+)-1-[4-[[2-(2,4-dichlorophenyl)- 2-[(1H-1,2,4-triazol-1-yl]methyl-1,3-dioxolane-4-yl]methyl]phenyl]-4-(1-methylethyl)piperazine, (2R,4S)-(+)-terconazole.

To a suspension of NaH (60-65% dispersion in paraffin, 36 mg, 0.90 mmol) in anhydrous DMSO (8 ml), 4-(4-hydroxyphenyl) -1 - ( 1-methyle thyl ) p iper az ine ( 193 mg , 0 . 88 mmol ) is added and the mixture is stirred for 1 hour at room temperature. Then, (2R,4R)-(+)-IV (Ar = 2,4-dichlorophenyl, Y = N, R = CH₃ ) is added (180 mg, 0.44 mmol) and the mixture is heated at 80°C for 4 hours. The reaction mixture is allowed to cool to room temperature, diluted with water (20 ml) and extraoteo with CH₂Cl₂ (3 × 25 ml). The combined organic phases are washed with 5N NaOH (3 × 25 ml) and water (3 × 25 ml dried with Na₂SO₄ and the solvent is evaporated of: under vacuum. The oily residue thus obtained is crystallized from diisopropyl ether to give (2R,4S)-(+)-terconazole ((2R,4S)-V, Ar = 2,4-cichlorophenyl, Y = N, Z = CH(CH₃)₂) (140 mg, 59 % yield) as a white solid, m.p. 72-74'C, [α]_D ²⁰ = + 11,05 (c = 0.4, CHCl₃).

IR (KBr), ʋ : 1585, 1512, 1454, 1380, 1270, 1239, 1137, 1048, 979, 820, 675 cm^-1.

¹H-NMR (200 MHz, CDCl₃), δ : 1.11 [d, J=6.5 Hz, 5H, (CH₃)₂CH], 2.73 [m, 5H, 3-H₂, 5-H₂ and (CH₃)₂CH], 3.49

(dd, J=9.6 Hz, J'=6.3 Hz, 1H), 3.80 (m, 2H ) and 3.91

(dd, J=8.2 Hz, J'=6.6 Hz, 1H) (4' '-CH₂ and 5' '-H₂), 4.35

(m, 1H, 4' '-H), 4.74 (d, J=14.6 Hz, 1H) and 4.84 (d, J=14.6 Hz, 1H) (CH₂-N), 6.76 [d, J=9.0 Hz, 2H, C2'(6')- H], 6.88 [d, J=9.0 Hz, 2H, C3'(5')-H], 7.24 (dd, J=8.5

Hz, J'=2.0 Hz, 1H, 5'''-H), 7.46 (d, J=2.0 Hz, 1H,

3"'-H), 7.56 (d, J=8.5 Hz, 1H, 6"'-H), 7.89 (s, 1 H) and

8.20 (s, 1H) (triazole 3-H and 5-H).

http://www.google.com/patents/WO1996029325A1?cl=en

AZERBAIJAN

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Caucasus Mountains in northern Azerbaijan.

Justice for Khojaly

Bibi Heybat Mosque

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