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

HRID 578869Notes

Reaction equation

HRID 578869 reaction equation
[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

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-0eaed2b838154c7f8c8cb4e0418a5899
Source dataset
uspto-grants-2015_05
Patent number
US09040708B2

Reaction notes

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