Reacción #67581

Ecuación de reacción

NaBH(OAc)3

lithium hydroxide

5-(3,3-Dimethyl-but-1-ynyl)-3-[(4-methyl-cyclohexanecarbonyl)-(4-oxo-cyclohexyl)-amino]-thiophene-2-carboxylic acid methyl ester

N-Methyl-N-thiazol-2-yl-hydrazine

NaHCO3

AcOH

→

title compound

Rendimiento 14.7%

5-(3,3-Dimethyl-but-1-ynyl)-3-{(4-methyl-cyclohexanecarbonyl)-[4-(N′-methyl-N′-thiazol-2-yl-hydrazino)-cyclohexyl]-amino}-thiophene-2-carboxylic acid

Rendimiento 14.7%

Disolventes

brine

water

MeOH

DCE

Condiciones de reacción

Tratamiento posterior

1. 1
   Extracciónthe crude product was extracted with ethyl acetate (2×20 mL)
2. 2
   ConcentraciónThe combined organic layers were concentrated
3. 3
   workup.DISSOLUTIONthe crude material was dissolved in a 3:2:1 mixture of THF
4. 4
   Temperaturaheated to 60 deg C
5. 5
   workup.WAITfor 1 hours
6. 6
   OtroThe residue was purified by HPLC (Gemini column, 35% acetonitrile
7. 7
   workup.ADDITIONwater, 2 min, 35-50% acetonitrile:water, 2 min, 50-100% acetonitrile: water 13 min, both solvents containing 0.1% trifluoroacetic acid)

Procedimiento

A mixture of 5-(3,3-Dimethyl-but-1-ynyl)-3-[(4-methyl-cyclohexanecarbonyl)-(4-oxo-cyclohexyl)-amino]-thiophene-2-carboxylic acid methyl ester (200 mg, 0.44 mmol) and N-Methyl-N-thiazol-2-yl-hydrazine (112 mg, 0.87 mmol) in DCE (4 mL) was treated with AcOH (200 μL, 3.0 mmol) followed by NaBH(OAc)3 (120 mg, 0.57 mmol) in two portions. After 5 h, NaHCO3 (saturated aqueous solution, 3 mL) was added to the mixture, followed by brine (20 mL), and the crude product was extracted with ethyl acetate (2×20 mL). The combined organic layers were concentrated and the crude material was dissolved in a 3:2:1 mixture of THF:MeOH:water (20 mL), treated with lithium hydroxide (2.2 mmol, 92 mg) and heated to 60 deg C. for 1 hours. The residue was purified by HPLC (Gemini column, 35% acetonitrile:water, 2 min, 35-50% acetonitrile:water, 2 min, 50-100% acetonitrile: water 13 min, both solvents containing 0.1% trifluoroacetic acid). This resulted in 36 mg of the title compound as its trans isomer (TFA salt): MS (m/z): 557.2 [M−H]+; HPLC retention time: 3.43 min (2-98% acetonitrile:water with 0.05% trifluoroacetic acid) and 8 mg of the title compound as its cis isomer (TFA salt): MS (m/z): 557.2 [M−H]+; HPLC retention time: 3.41 min (2-98% acetonitrile:water with 0.05% trifluoroacetic acid).

Fuente