Triethylamine → 1-(2-[4-(6-Trifluoromethyl-benzo[b]thiophen-3-yl)-piperazin-1-yl]-ethyl}-cyclopropanecarboxylic acid (3-imidazol-1-yl-propyl)-amide

HRID 501350Notes

Reaction equation

HRID 501350 reaction equation
[F:1][C:2]([F:27])([F:26])[C:3]1[CH:4]=[CH:5][C:6]2[C:10]([N:11]3[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][C:19]4([C:22]([OH:24])=O)[CH2:21][CH2:20]4)[CH2:13][CH2:12]3)=[CH:9][S:8][C:7]=2[CH:25]=1.C(Cl)(=O)C(Cl)=O.[NH2:34][CH2:35][CH2:36][CH2:37][N:38]1[CH:42]=[CH:41][N:40]=[CH:39]1.C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>ClCCl.CN(C=O)C>[N:38]1([CH2:37][CH2:36][CH2:35][NH:34][C:22]([C:19]2([CH2:18][CH2:17][N:14]3[CH2:15][CH2:16][N:11]([C:10]4[C:6]5[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:27])[F:26])=[CH:25][C:7]=5[S:8][CH:9]=4)[CH2:12][CH2:13]3)[CH2:20][CH2:21]2)=[O:24])[CH:42]=[CH:41][N:40]=[CH:39]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 787361H-Imidazole-1-propanamineHCID 516892Sodium BicarbonateHCID 231124271-{2-[4-(6-Trifluoromethyl-benzo[b]thiophen-3-yl)-piperazin-1-yl]-ethyl}-cyclopropanecarboxylic acid

Product 1

HCID 588177541-(2-[4-(6-Trifluoromethyl-benzo[b]thiophen-3-yl)-piperazin-1-yl]-ethyl}-cyclopropanecarboxylic acid (3-imidazol-1-yl-propyl)-amideYield 38%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

A suspension of 0.17 g (0.39 mmol) of 1-{2-[4-(6-trifluoromethyl-benzo[b]thiophen-3-yl)-piperazin-1-yl]-ethyl}-cyclopropanecarboxylic acid in 10 mL dichloromethane under nitrogen was treated with 1 mL of oxalyl chloride followed by 3 drops of DMF. After 2 hours the reaction was concentrated to a slurry, diluted with 10 mL DMF and treated with 0.10 g (0.78 mmol) of 1-(3-aminopropyl)imidazole followed by 0.12 g (1.2 mmol) of triethylamine. After 12 hours the reaction was poured into aqueous saturated sodium bicarbonate and extracted with ethyl acetate. The organic layer was separated, dried and concentrated to deliver an oil. Chromatographic purification gave 0.075 g (38%) of the desired final product as an oil.

Workup

  1. concentrationAfter 2 hours the reaction was concentrated to a slurry
  2. additiondiluted with 10 mL DMF
  3. extractionextracted with ethyl acetate
  4. customThe organic layer was separated
  5. customdried
  6. concentrationconcentrated
  7. customChromatographic purification

Sources & evidence

ORD record
ord-c357677a2890472a8329ad80fc9ec245
Source dataset
uspto-grants-2010_08
Patent number
US07772252B2

Reaction notes

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