Triethylamine → (3-Chloro-1H-indol-5-yl)-(4-isopropyl-piperazin-1-yl)-methanone

HRID 2113469

Reaction equation

HRID 2113469 reaction equation
CO[C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[C:8]2[Cl:14])=[O:4].O[Li].O.[CH3:18][CH:19]([N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1)[CH3:20].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(CC)CC.C([O-])(O)=O.[Na+]>C1COCC1.CO.O.CN(C=O)C>[Cl:14][C:8]1[C:7]2[C:11](=[CH:12][CH:13]=[C:5]([C:3]([N:24]3[CH2:25][CH2:26][N:21]([CH:19]([CH3:20])[CH3:18])[CH2:22][CH2:23]3)=[O:4])[CH:6]=2)[NH:10][CH:9]=1

Participants

11

Reactant 6

HCID 8471TriethylamineHCID 780131-IsopropylpiperazineHCID 168937Lithium hydroxide, monohydrateHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 219987283-Chloro-1H-indole-5-carboxylic acid methyl ester

Product 1

HCID 68622026(3-Chloro-1H-indol-5-yl)-(4-isopropyl-piperazin-1-yl)-methanoneYield 44%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 1.05 g (5 mmol) 3-Chloro-1H-indole-5-carboxylic acid methyl ester and 1.05 g (25 mmol) LiOH.H2O in THF, methanol, water was stirred at 50° C. for 4 h. The mixture was evaporated to dryness and the corresponding acid was used without further purification in the subsequent step. 0.77 g (6 mmol) 1-(2-propyl)-piperazine, 2.4g (7.5 mmol) TBTU, 2.5 g (25 mmol) NEt3 and 20 mL DMF was added and the mixture was stirred at room temperature for 4 h. 1N NaHCO3 was added and the mixture was extracted with DCM. The combined organic layers were dried with MgSO4, filtered and evaporated. The residue was purified by flash column chromatography on silica eluting with a gradient formed from heptane, ethyl acetate, methanol and NEt3. The combined product fractions were evaporated to yield 0.67 g (44%) of the title compound as light brown solid. MS(m/e): 306.3 (MH+).

Workup

  1. customThe mixture was evaporated to dryness
  2. customthe corresponding acid was used without further purification in the subsequent step
  3. stirringthe mixture was stirred at room temperature for 4 h
  4. extractionthe mixture was extracted with DCM
  5. dry with materialThe combined organic layers were dried with MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by flash column chromatography on silica eluting with a gradient
  9. customformed from heptane, ethyl acetate, methanol and NEt3
  10. customThe combined product fractions were evaporated

Sources & evidence

ORD record
ord-7c4df635f0e34bab99499a35d4c8f42a
Source dataset
uspto-grants-2008_10
Patent number
US07432255B2

Linked notes

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