ChemicalBook CAS DataBase List Montelukast Bis-sulfide (Mixture of Diastereomers)

Montelukast Bis-sulfide (Mixture of Diastereomers) synthesis

13synthesis methods

Product Name:Montelukast Bis-sulfide (Mixture of Diastereomers)
CAS Number:1187586-61-3
Molecular formula:C41H46ClNO5S2
Molecular Weight:732.39

162515-68-6 Synthesis

2-[1-(Mercaptomethyl)cyclopropyl]acetic acid

162515-68-6
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151767-02-1 Synthesis

151767-02-1
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$8.00/50mg

Montelukast Bis-sulfide (Mixture of Diastereomers)

1187586-61-3
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1187586-58-8
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Yield:-

Reaction Conditions:

Stage #1: 1-(sulfanylmethyl)cyclopropaneacetic acidwith sodium t-butanolate;PEG-600 in toluene;Inert atmosphere;
Stage #2: Montelukast sodium in tetrahydrofuran;toluene at 20;Inert atmosphere;

Steps:

12

EXAMPLE 12 (Preparation of the standards of 2-[(R)-l-[[[l-[3-[2-(7-chloro-2-quinolinyl)- (S)- 1 -( { [ 1 -(carboxymethyl)cyclopropyl]methyl} thio)ethyl]phenyl]-3-[2-( 1 -hydroxy- 1 - methylethyl)phenyl]-propyl]thio]methyl]cyclopropane]acetic acid and 2-[(R)-l-[[[l-[3-[2-(7- chloro-2-quinolinyl)-(R)-l-({[l-(carboxymethyl)cyclopropyl]-methyl}thio)ethyl]phenyl]-3-[2- (l-hydroxy-l-methyl-ethyl)phenyl]propyl]thio]methyl]cyclopropane]acetic acid)To [l-(mercaptomethyl)cyclopropyl] acetic acid (0.7 g) toluene (20 ml), sodium tert-butoxide (0.85 g) and a solution of 2.6 g of PEG-600 in 3 ml of toluene were added under argon atmosphere. Then, a solution of montelukast sodium (2.72 g) in 15 ml of tetrahydrofuran was added dropwise to the stirred mixture. The obtained mixture was stirred at the laboratory temperature and under argon atmosphere for 30 days. Then, toluene (100 ml) was added and 45 ml of the liquid was removed by vacuum distillation. The residue was washed with a solution of tartaric acid and water. The organic phase was dried over sodium sulfate and concentrated to the volume of 30 ml after filtration of the desiccant. To the concentrated residue 3 ml of acetonitrile, 0.5 ml of isopropylamine and gradually 30 ml of heptane were added. The separated suspension of the salt of montelukast with isopropylamine was filtered off and the filtered mother liquor was concentrated in vacuum. 0.4 g of an oily product were obtained, which, according to HPLC, contained 70% of a mixture of montelukast diastereoisomers I and II. The standards of both the diastereoisomers in the form of free acids were obtained in the quantities of approx. 80 mg with the use of the Waters auto-purification system (description - see analytic methods).Montelukast diastereoisomer I:¹H NMR (500 MHz, CDCl₃), δ (ppm): 0.38 (m, 2H) ; 0.41-0.48 (m, 4H); 0.56(m, 2H); 1.60(s, 3H); 1.61(s, 3H); 2.00(d, IH); 2.40(d, IH); 2.16(q,2H); 2.33(d, IH); 2.43(d, IH); 2.35(d, IH); 2.55(d, IH); 2.37(d, IH); 2.49(d, IH); 2.97(q, 2H); 3.37(dd, IH); 3.62(dd, IH); 3.93(t, IH); 4.29(dd, IH); 7.1 l(m, IH); 7.17(m, 2H); 7.23(m, IH); 7.24(m, IH); 7.28(m, IH); 7.30(m, IH); 7.38(d, IH); 7.4(dd, lH);7.70(d, IH); 8.08(d, IH); 8.1 l(d, IH). ¹³C NMR (500 MHz, CDCl₃), δ (ppm): 12.2; 12.5; 12.6; 17.1; 17.7; 31.6; 31.8; 32.4; 38.1; 39.2; 39.3; 40.0; 41.2; 45.4; 50.7; 51.2; 123.2; 125.4; 125.5; 126.1; 126.2; 126.8; 127.3; 127.5; 128.2; 128.8; 129.4; 131.8; 135.9; 139.7; 140.7; 142.3; 142.6; 144.6; 147.2; 161.0; 175.7; 175.9. MS: 432,2586 (M+l)⁺.Montelukast diastereoisomer II:¹H NMR (500 MHz, CDCl₃), δ (ppm): 0.36-,62(m, 8H); 1.56(s, 3H); 1.57(s, 3H); 1.98(m, IH);2.13(m, IH); 2.00(m, IH); 2.46(m, IH); 2.20(d, IH); 2.65(d, IH); 2.36(d, IH); 2.48(d, IH); 2.77(m, IH); 2.96(m, IH); 3.29(dd, IH); 3.68(dd, IH); 3.95(t, IH) 4.36(dd, IH); 7.09(m, IH);7.10(m, IH);; 7.16(dd, IH); 7.18(dd, IH); 7.27(m, IH); 7.28(m, IH); 7.30(m, IH);; 7.35(m,IH); 7.36(m, IH); 7.40 (dd, IH); 7.61(d, IH); 8.02(d, IH); 8.09(d, IH).¹³C NMR (500 MHz, CDCl₃), δ (ppm): 12.1; 12.3; 12.5; 12.8; 16.6; 17.0; 31.6; 31.7; 32.1;38.8; 39.1 ; 40.0; 40.5; 45.7; 50.3; 51.0; 74.3; 123.3; 125.3; 125.4; 125.6; 125.9; 126.8; 127.1; 127.2; 127.4; 128.2; 129.1; 131.7; 135.9; 136.7; 140.4; 142.4; 142.7; 144.8; 147.3; 161.0;175.9; 176.2.MS: 432,2591 (M+l)⁺.