1-Isopropylpiperazine → 5-(4-Isopropyl-piperazine-1-carbonyl)-1H-indole-2-carboxylic acid ethyl ester

HRID 1992453Notes

Reaction equation

HRID 1992453 reaction equation
[CH3:1][CH2:2][O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([C:15]([OH:17])=O)=[CH:10][CH:9]=2)=[O:5].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[CH:40]([N:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1)([CH3:42])[CH3:41].C(N(CC)C(C)C)(C)C.C(=O)(O)[O-].[Na+]>CN(C)C=O>[CH2:2]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([C:15]([N:46]1[CH2:47][CH2:48][N:43]([CH:40]([CH3:42])[CH3:41])[CH2:44][CH2:45]1)=[O:17])=[CH:10][CH:9]=2)=[O:5])[CH3:1]

Participants

7

Reactant 5

HCID 780131-IsopropylpiperazineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 180713652-(Ethoxycarbonyl)-1H-indole-5-carboxylic acid

Product 1

HCID 685341345-(4-Isopropyl-piperazine-1-carbonyl)-1H-indole-2-carboxylic acid ethyl esterYield 74.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5.0 g (21.4 mmol) 1H-indole-2,5-dicarboxylic acid 2-ethyl ester (prepared according to J. Org. Chem. 1953, 18, 345-57) in 50 mL N,N-dimethylformamide, were added 8.6 g (26.8 mmol) O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate. After 10 min., 3.44 g (26.8 mmol) 1-isopropylpiperazine and 18.3 mL (13.9 g, 107.4 mmol) N,N-diisopropylethylamine were added. After 45 min. the reaction mixture was poured into saturated aqueous sodium bicarbonate solution and extracted three times with ethyl acetate. The combined organic layers were washed three times with water, brine, dried over magnesium sulfate, filtered and evaporated. The residue was flash-chromatographed on silica gel with dichloromethane:methanol:ammonia (9:1:0.1 v/v) and ethyl acetate:methanol (9:1) as eluant to give 5.5 g (74%) of the desired compound as a light yellow solid. MS (ISP): 344.3 (M+H)+.

Workup

  1. extractionextracted three times with ethyl acetate
  2. washThe combined organic layers were washed three times with water, brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was flash-chromatographed on silica gel with dichloromethane:methanol:ammonia (9:1:0.1 v/v) and ethyl acetate:methanol (9:1) as eluant

Sources & evidence

ORD record
ord-ff208bc0d7844337b08afc65f1e9b776
Source dataset
uspto-grants-2010_01
Patent number
US07648979B2

Reaction notes

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