6-Methyl-[1,2,4]triazolo[1,5-A]pyrimidine-2-carbaldehyde → 1-(4-{2-[2-Cyclopentyl-5-(6-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-ylmethyl)-4,6-dioxo-tetrahydro-pyran-2-yl]-ethyl}-2-fluoro-phenyl)-cyclopropanecarbonitrile

HRID 858631노트

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HRID 858631 반응식
[CH:1]1([C:6]2([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]4([C:25]#[N:26])[CH2:24][CH2:23]4)=[C:18]([F:27])[CH:17]=3)[CH2:11][C:10](=[O:12])[CH2:9][C:8](=[O:13])[O:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:28][C:29]1[CH:30]=[N:31][C:32]2[N:33]([N:35]=[C:36]([CH:38]=O)[N:37]=2)[CH:34]=1>CO>[CH:1]1([C:6]2([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]4([C:25]#[N:26])[CH2:23][CH2:24]4)=[C:18]([F:27])[CH:17]=3)[CH2:11][C:10](=[O:12])[CH:9]([CH2:38][C:36]3[N:37]=[C:32]4[N:31]=[CH:30][C:29]([CH3:28])=[CH:34][N:33]4[N:35]=3)[C:8](=[O:13])[O:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1

참가 물질

4

반응물 2

HCID 587626196-Methyl-[1,2,4]triazolo[1,5-A]pyrimidine-2-carbaldehydeHCID 587627061-{4-[2-(2-Cyclopentyl-4,6-dioxo-tetrahydro-pyran-2-yl)-ethyl]-2-fluoro-phenyl}-cyclopropanecarbonitrile

생성물 1

HCID 113867551-(4-{2-[2-Cyclopentyl-5-(6-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-ylmethyl)-4,6-dioxo-tetrahydro-pyran-2-yl]-ethyl}-2-fluoro-phenyl)-cyclopropanecarbonitrile

시약·촉매·용매 1

HCID 887Methanol용매

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온도
-10 °C

실험 절차

A solution of 1-{4-[2-(2-cyclopentyl-4,6-dioxo-tetrahydro-pyran-2-yl)-ethyl]-2-fluoro-phenyl}-cyclopropanecarbonitrile (568 mg, 1.54 mmol) in anhydrous MeOH (6.0 mL) was treated with 6-methyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehyde (324 mg, 2.0 mmol), followed by borane-dimethylamine complex (118 mg, 2.0 mmol) at room temperature. The reaction was stirred for 1 hour before it was cooled to −10° C. for 2 hours. The precipitate was removed by filtration, and the filtrate was concentrated to an oil. The oil was purified by flash chromatography (50 g SiO2, 1:3->1:0 (93.5% ethyl acetate, 6% methanol, 0.5% acetic acid): (81.5% hexanes, 12% ethyl acetate, 6% methanol, 0.5% acetic acid)) to give the desired product as an oil. It was further purified by crystallization from ethyl acetate/hexanes to give a white powder (146 mg, 18%). 1H NMR (400 MHz, CDCl3) δ: 1.41–1.64 (m, 8 H), 1.84–1.88 (m, 2 H), 2.22–2.28 (m, 2 H), 2.42 (s, 3 H), 2.49–2.59 (m, 4 H), 2.65–2.74 (m, 3 H), 3.97–4.05 (m, 2 H), 6.72–6.82 (m, 2 H), 7.05–7.10 (m, 1 H), 8.55 (s, 1 H), 8.67 (s, 1 H).

후처리

  1. customfollowed by borane-dimethylamine complex (118 mg, 2.0 mmol) at room temperature
  2. customThe precipitate was removed by filtration
  3. concentrationthe filtrate was concentrated to an oil
  4. customThe oil was purified by flash chromatography (50 g SiO2, 1:3->1:0 (93.5% ethyl acetate, 6% methanol, 0.5% acetic acid): (81.5% hexanes, 12% ethyl acetate, 6% methanol, 0.5% acetic acid))

출처 및 근거

ORD 기록
ord-caea795731994775a4b99d9d54d8df3f
출처 데이터셋
uspto-grants-2006_12
특허 번호
US07148226B2

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