반응 #67588

반응 방정식

4-[N′-[2-carboxy-5-(3,3-dimethyl-but-1-ynyl)-thiophen-3-yl]-N-methyl-N′-(4-methyl-cyclohexanecarbonyl)-hydrazino]-piperidine-1-carboxylic acid tert-butyl ester

TFA

→

title compound

5-(3,3-dimethyl-but-1-ynyl)-3-[N′-methyl-N-(4-methyl-cyclohexanecarbonyl)-N′-piperidin-4-yl-hydrazino]-thiophene-2-carboxylic acid

용매

toluene

반응 조건

후처리

1. 1
   온도After cooling
2. 2
   농축the mixture was concentrated
3. 3
   기타a portion of this crude material was purified by HPLC (Gemini column, 35% acetonitrile
4. 4
   workup.ADDITIONwater, 2 min, 35-50% acetonitrile:water, 2 min, 50-95% acetonitrile: water 13 min, both solvents containing 0.1% trifluoroacetic acid)

실험 절차

Crude 4-[N′-[2-carboxy-5-(3,3-dimethyl-but-1-ynyl)-thiophen-3-yl]-N-methyl-N′-(4-methyl-cyclohexanecarbonyl)-hydrazino]-piperidine-1-carboxylic acid tert-butyl ester (220 mg, 500 mmol) (Example 127) was treated with TFA (3 mL, 4.6 mmol) at 60° C. for 10 min. After cooling, toluene (2-3 mL) was added and the mixture was concentrated, this was repeated several times, and a portion of this crude material was purified by HPLC (Gemini column, 35% acetonitrile:water, 2 min, 35-50% acetonitrile:water, 2 min, 50-95% acetonitrile: water 13 min, both solvents containing 0.1% trifluoroacetic acid). This resulted in 20 mg of the title compound as a white powder (bis-TFA salt): MS (m/z): 460.2 [M−H]+; HPLC retention time: 3.15 min (2-98% acetonitrile:water with 0.05% trifluoroacetic acid).

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