1-Hydroxybenzotriazole → 3-chloro-N-[[1-[3-chloro-5-[2-(trifluoromethyl)cyclopropyl]-2-pyridyl]cyclopropyl]methyl]pyrazine-2-carboxamide

HRID 578869ノート

反応式

HRID 578869 の反応式
[Cl:1][C:2]1[C:3]([C:15]2([CH2:18][NH2:19])[CH2:17][CH2:16]2)=[N:4][CH:5]=[C:6]([CH:8]2[CH2:10][CH:9]2[C:11]([F:14])([F:13])[F:12])[CH:7]=1.Cl.C(N=C=NCCCN(C)C)C.[Cl:32][C:33]1[C:34]([C:39](O)=[O:40])=[N:35][CH:36]=[CH:37][N:38]=1.ON1C2C=CC=CC=2N=N1>ClCCl.O.C(N(CC)CC)C>[Cl:32][C:33]1[C:34]([C:39]([NH:19][CH2:18][C:15]2([C:3]3[C:2]([Cl:1])=[CH:7][C:6]([CH:8]4[CH2:10][CH:9]4[C:11]([F:14])([F:12])[F:13])=[CH:5][N:4]=3)[CH2:17][CH2:16]2)=[O:40])=[N:35][CH:36]=[CH:37][N:38]=1

参加物

8

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 15019003-Chloro-2-pyrazine-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 89544472[1-[3-Chloro-5-[2-(trifluoromethyl)cyclopropyl]-2-pyridyl]cyclopropyl]methanamine

生成物 1

HCID 715589873-chloro-N-[[1-[3-chloro-5-[2-(trifluoromethyl)cyclopropyl]-2-pyridyl]cyclopropyl]methyl]pyrazine-2-carboxamide収率 73.8%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 8471Triethylamine溶媒

反応条件

温度
0 °C

実験手順

147 mg [1-[3-chloro-5-[2-(trifluoromethyl)cyclopropyl]-2-pyridyl]cyclopropyl]methanamine (step 3) was dissolved in 3 ml of dichloromethane and 0.142 ml triethylamine was added. After cooling to 0° C., 193 mg 3-(ethyliminomethyleneamino)-N,N-dimethyl-propan-1-amine hydrochloride, 84 mg 3-chloropyrazine-2-carboxylic acid and 141 mg 1-hydroxybenzotriazole were added. The mixture was stirred overnight at ambient temperature. Then water was added. The layers were separated, the organic layer was dried over anhydrous sodium sulphate, filtered and concentrated. Crude material was obtained as an orange oil, which was purified by flash chromatography on silica gel with heptane/ethyl acetate as a solvent. Thus, 161 mg of 3-chloro-N-[[1-[3-chloro-5-[2-(trifluoromethyl)cyclopropyl]-2-pyridyl]cyclopropyl]methyl]pyrazine-2-carboxamide was obtained as a yellow sticky solid. 1H-NMR (CDCl3): 8.42 ppm (d, 1H), 8.38 ppm (d, 1H), 8.18 ppm (s, 1H), 7.78 ppm (s, 1H, broad), 7.31 ppm (s, 1H), 3.66 ppm (d, 1H), 2.26 ppm (m, 1H), 1.78 ppm (m, 1H), 1.57 ppm (m, 1H), 1.39 ppm (m, 1H), 1.18 ppm (m, 4H).

後処理

  1. customThe layers were separated
  2. dry with materialthe organic layer was dried over anhydrous sodium sulphate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customCrude material was obtained as an orange oil, which
  6. customwas purified by flash chromatography on silica gel with heptane/ethyl acetate as a solvent

出典と根拠

ORDレコード
ord-0eaed2b838154c7f8c8cb4e0418a5899
出典データセット
uspto-grants-2015_05
特許番号
US09040708B2

反応ノート

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