Diisopropylethylamine → [6-Bromo-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-[4-(piperidine-1-sulfonyl)-piperazin-1-yl]-methanone

HRID 1786451Notes

Reaction equation

HRID 1786451 reaction equation
Cl.[Br:2][C:3]1[CH:11]=[C:10]2[C:6]([CH:7]=[C:8]([C:12](O)=[O:13])[NH:9]2)=[CH:5][C:4]=1[O:15][CH:16]1[CH2:21][CH2:20][N:19]([CH:22]([CH3:24])[CH3:23])[CH2:18][CH2:17]1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[N:47]1([S:53]([N:56]2[CH2:61][CH2:60][NH:59][CH2:58][CH2:57]2)(=[O:55])=[O:54])[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]1.C(N(CC)C(C)C)(C)C.C(=O)(O)[O-].[Na+]>CN(C)C=O>[Br:2][C:3]1[CH:11]=[C:10]2[C:6]([CH:7]=[C:8]([C:12]([N:59]3[CH2:58][CH2:57][N:56]([S:53]([N:47]4[CH2:48][CH2:49][CH2:50][CH2:51][CH2:52]4)(=[O:55])=[O:54])[CH2:61][CH2:60]3)=[O:13])[NH:9]2)=[CH:5][C:4]=1[O:15][CH:16]1[CH2:21][CH2:20][N:19]([CH:22]([CH3:23])[CH3:24])[CH2:18][CH2:17]1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 2855011-(1-Piperidinylsulfonyl)piperazineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 670179306-bromo-5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carboxylic acid hydrochloride

Product 1

HCID 68565981[6-Bromo-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-[4-(piperidine-1-sulfonyl)-piperazin-1-yl]-methanoneYield 56%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 0.5 g (1.20 mmol) 6-bromo-5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carboxylic acid hydrochloride in 8 mL N,N-dimethylformamide, 0.48 g (1.50 mmol) O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate, 0.31 g (1.33 mmol) 1-(piperidin-1-yl-sulfonyl)-piperazine and 1.0 mL (0.77 g, 6.0 mmol) N,N-diisopropylethylamine were added. After 2 h the solution was poured on 10% aqueous sodium bicarbonate solution, the phases were separated and the aqueous phase was extracted three times with ethyl acetate. The combined organic layers were washed three times with water followed by brine, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash chromatography twice on silica gel using a gradient of dichloromethane: methanol (100:0 to 50:50 v/v) as eluant, to afford 0.4 g (56%) of the title compound as a light-yellow foam.

Workup

  1. customthe phases were separated
  2. extractionthe aqueous phase was extracted three times with ethyl acetate
  3. washThe combined organic layers were washed three times with water
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by flash chromatography twice on silica gel using a gradient of dichloromethane: methanol (100:0 to 50:50 v/v) as eluant

Sources & evidence

ORD record
ord-1e436c8e703f4c7799339d289b3f6850
Source dataset
uspto-grants-2009_03
Patent number
US07507736B2

Reaction notes

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