Triethylamine → 4-[2-(Inden-1-yl)ethyl]-1-(4-aminocarbonylphenyl)piperazine

HRID 368852Notes

Reaction equation

HRID 368852 reaction equation
[CH:1]1([CH2:10][CH2:11]O)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.CN(C1C=CC=CN=1)C.C(N(CC)CC)C.CS(Cl)(=O)=O.[N:34]1([C:40]2[CH:45]=[CH:44][C:43]([C:46]([NH2:48])=[O:47])=[CH:42][CH:41]=2)[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1.C(N(C(C)C)CC)(C)C>O1CCCC1.O.C(O)CO>[CH:1]1([CH2:10][CH2:11][N:37]2[CH2:36][CH2:35][N:34]([C:40]3[CH:41]=[CH:42][C:43]([C:46]([NH2:48])=[O:47])=[CH:44][CH:45]=3)[CH2:39][CH2:38]2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

Participants

10

Reactant 6

HCID 8471TriethylamineHCID 218852-DimethylaminopyridineHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 111065094-(1-Piperazinyl)benzamideHCID 232887512-(1H-Inden-1-yl)ethan-1-ol

Product 1

HCID 232887964-[2-(Inden-1-yl)ethyl]-1-(4-aminocarbonylphenyl)piperazine

Reagents, catalysts & solvents 3

HCID 174Ethylene GlycolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-(inden-1-yl)ethanol (CXVI-B, EXAMPLE 86, 0.8 g, 5 mmol), dimethylaminopyridine (0.02 g, 0.2 mmol) and triethylamine (1.7 ml, 12.5 mmol) in tetrahydrofuran (10 ml) is cooled to 0° and methanesulfonyl chloride (0.43 ml, 5.5 mmol) is added dropwise. After 45 min, 4-(piperazinyl)benzenecarboxamide (LXV, 1.23 g, 6 mmol), diisopropylethylamine (1.0 ml, 6 mmol) and ethyleneglycol (10 ml) are added and heated at 85° for 60 hr. The mixture is diluted with water and extracted with methylene chloride. The organic phase is separated, washed with saline, dried (magnesium sulfate), filtered and concentrated. Crystallization from ethyl acetate gives the title compound, mp 207°; NMR (CDCl3, TMS) 7.75-6.90, 6.28 and 3.39-2.68 δ.

Workup

  1. temperatureis cooled to 0°
  2. temperatureheated at 85° for 60 hr
  3. extractionextracted with methylene chloride
  4. customThe organic phase is separated
  5. washwashed with saline
  6. dry with materialdried (magnesium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customCrystallization from ethyl acetate

Sources & evidence

ORD record
ord-6e96bca7a221445eb84963b10242a22e
Source dataset
uspto-grants-2000_10
Patent number
US06133446

Reaction notes

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