JPWO2021226269A5 - - Google Patents

Description

１－（（２－（トリメチルシリル）エトキシ）メチル）－１Ｈ－ピラゾール－５－カルボニトリル（５．４０ｇ、２４．２ｍｍｏｌ）のＴＨＦ（５０ｍＬ）溶液に、ＬｉＴＭＰ・ＭｇＣｌ_２（１．０ＭのＴＨＦ溶液、３６．３ｍＬ、３６．３ｍｍｏｌ）を窒素下、－１６℃で滴下した。得られた溶液を－１６℃で１時間攪拌した。次いで、Ｎ，Ｎ－ジメチルホルムアミド（３．７ｍＬ、４８．４ｍｍｏｌ）を添加し、その混合物を１時間撹拌した。この反応物にブラインを添加してクエンチし、ＥｔＯＡｃ（２ｘ３０ｍＬ）で抽出し、乾燥し、濃縮した。その残渣をフラッシュクロマトグラフィー（シリカゲル、０→５％酢酸エチルを含む石油エーテル）により精製して、３－ホルミル－１－（（２－（トリメチルシリル）エトキシ）メチル）－１Ｈ－ピラゾール－５－カルボニトリル（３．４ｇ、６０％）を褐色液体として得た。ＬＣ／ＭＳ （ＥＳＩ） ｍ／ｚ： ２５２ ［Ｍ＋Ｈ］^＋． Synthesis of 3-formyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole-5-carbonitrile

To a solution of 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole-5-carbonitrile (5.40 g, 24.2 mmol) in THF (50 mL) was added LiTMP.MgCl ₂ (1.0 M in THF, 36.3 mL, 36.3 mmol) dropwise under nitrogen at −16° C. The resulting solution was stirred at −16° C. for 1 h. N,N-dimethylformamide (3.7 mL, 48.4 mmol) was then added and the mixture was stirred for 1 h. The reaction was quenched by the addition of brine, extracted with EtOAc (2×30 mL), dried and concentrated. The residue was purified by flash chromatography (silica gel, 0→5% ethyl acetate in petroleum ether) to give 3-formyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole-5-carbonitrile (3.4 g, 60%) as a brown liquid. LC/MS (ESI) m/z: 252 [M+H] ⁺ .

Claims (6)

A compound of the formula:

or a pharma- ceutically acceptable salt thereof. A compound of the formula:

2. The compound of claim 1, A compound of the formula:

2. The pharma- ceutically acceptable salt of claim 1, which is a pharma- ceutically acceptable salt of A pharmaceutical composition comprising the compound of claim 1 and/or a pharma- ceutical acceptable salt thereof. A pharmaceutical composition comprising the compound of claim 2. A pharmaceutical composition comprising the pharma- ceutical acceptable salt of claim 3.