1H-CyclopentapyriMidine-1-acetic acid, 2-[[(4-fluorophenyl)Methyl]thio]-4,5,6,7-tetrahydro-4-oxo- synthesis

8synthesis methods

Product Name:1H-CyclopentapyriMidine-1-acetic acid, 2-[[(4-fluorophenyl)Methyl]thio]-4,5,6,7-tetrahydro-4-oxo-
CAS Number:356058-42-9
Molecular formula:C16H15FN2O3S
Molecular Weight:334.37

1349902-20-0 Synthesis

2,3,4,5,6,7-hexahydro-4-oxo-2-thioxo-1H-CyclopentapyriMidine-1-acetic acid

1349902-20-0
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352-11-4 Synthesis

352-11-4
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1H-CyclopentapyriMidine-1-acetic acid, 2-[[(4-fluorophenyl)Methyl]thio]-4,5,6,7-tetrahydro-4-oxo-

356058-42-9
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Yield:356058-42-9 97%

Reaction Conditions:

Stage #1: 2-(4-oxo-2-thioxo-2,3,4,5,6,7-hexahydro-1H-cyclopenta-[d]-pyrimidin-1-yl) acetic acid;1-chloromethyl-4-fluorobenzenewith sodium carbonate;sodium hydroxide in water;isopropyl alcohol at 40; for 2.5 h;
Stage #2: with formic acid in water;isopropyl alcohol at 20; for 2.5 h;Product distribution / selectivity;

Steps:

7

Example 7 - Alternative method for making (2-{[(4-Fluorophenyl)methyl]thio}-4-oxo-4,5,6,7- tetrahydro-lHcyclopenta[d]pyrimidin-l-yl)acetic acid) (4-Oxo-2-thioxo-2,3,4,5,6,7-hexahydro-lH- cyclopenta [ /]pyrimidin-l-yl)acetic acid (20.0 g, 1.0 eq) was slurried in a mixture of water (112 mL) and isopropyl alcohol (20 mL). NaOH solution (50.9% aqueous, 13.82 g, 1.99 eq) was added followed by a water line wash (10 mL) resulting in a solution. Then Na₂C0₃ (1.50 g, 0.16 eq) was charged and the solution was heated to 40+/-3° C. Thereafter 4-fluorobenzyl chloride (13.4 g, 1.05 eq) was added, followed by a line wash of isopropyl alcohol (12 mL) and the reaction mixture was stirred at 40+/-3° C until the reaction was deemed complete ( ~2.5 hours). The reaction mixture was cooled to 20+/-3° C and formic acid (2.4 g, 0.6 eq) was added resulting in crystallisation of the product within 30 minutes. A second charge of formic acid (6.9 g, 1.7 eq) was added over 1 hour and the slurry was stirred at 20+/-3° C for at least one hour. The slurry was filtered to isolate the product, which was washed twice with a mixture of water (32 mL) and isopropyl alcohol (8 mL), then with isopropyl alcohol (40 mL) and dried in vacuo at 50° C to yield the title compound as an off-white solid (28.6 g, 97%th). ¹H NM R (d₆ DMSO) δ 1.95 (2H, m), 2.57 (2H, t), 2.85 (2H, t), 4.4 (2H, s), 4.7 (2H, s), 7.15 (2H, dd), 7.45 (2H, dd), ~13.6 (1H, vbrs).

References:

WO2011/146494,2011,A1 Location in patent:Page/Page column 11

1417526-07-8
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356058-42-9
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References

4H-CyclopentapyriMidin-4-one, 2-[[(4-fluorophenyl)Methyl]thio]-1,5,6,7-tetrahydro- (9CI)

451487-18-6
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356058-42-9
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References

10472-24-9
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356058-42-9
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References

2-Mercapto-6,7-dihydro-3H-cyclopentapyriMidin-4(5H)-one

35563-27-0
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356058-42-9
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References