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

HRID 578869노트

반응식

HRID 578869 반응식
[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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 962Water용매HCID 6344Dichloromethane용매HCID 8471Triethylamine용매

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온도
0 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-0eaed2b838154c7f8c8cb4e0418a5899
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09040708B2

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