Methylamine → N-methyl-2-{4-[(2-{7-[methyl(2-thienylsulfonyl)amino]-1H-indol-2-yl}-1,3-thiazol-5-yl)methyl]piperazin-1-yl}acetamide

HRID 1994746Notes

Reaction equation

HRID 1994746 reaction equation
[CH3:1][N:2]([S:28]([C:31]1[S:32][CH:33]=[CH:34][CH:35]=1)(=[O:30])=[O:29])[C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]1[S:13][C:14]([CH2:17][N:18]3[CH2:23][CH2:22][N:21]([CH2:24][C:25](O)=[O:26])[CH2:20][CH2:19]3)=[CH:15][N:16]=1)=[CH:8]2.[N:36]1(O)[C:40]2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.CN.C(=O)([O-])O.[Na+]>CN(C)C=O.C1COCC1>[CH3:40][NH:36][C:25](=[O:26])[CH2:24][N:21]1[CH2:20][CH2:19][N:18]([CH2:17][C:14]2[S:13][C:12]([C:9]3[NH:10][C:11]4[C:7]([CH:8]=3)=[CH:6][CH:5]=[CH:4][C:3]=4[N:2]([CH3:1])[S:28]([C:31]3[S:32][CH:33]=[CH:34][CH:35]=3)(=[O:30])=[O:29])=[N:16][CH:15]=2)[CH2:23][CH2:22]1

Participants

8

Reactant 5

HCID 6329MethylamineHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 59135617{4-[(2-{7-[methyl(2-thienylsulfonyl)amino]-1H-indol-2-yl)-1,3-thiazol-5-yl)methyl]piperazin-1-yl}acetic acid

Product 1

HCID 59135775N-methyl-2-{4-[(2-{7-[methyl(2-thienylsulfonyl)amino]-1H-indol-2-yl}-1,3-thiazol-5-yl)methyl]piperazin-1-yl}acetamideYield 73.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of {4-[(2-{7-[methyl(2-thienylsulfonyl)amino]-1H-indol-2-yl}-1,3-thiazol-5-yl)methyl]piperazin-1-yl}acetic acid (0.200 g) in N,N-dimethylformamide (10 ml) were added 1H-1,2,3-benzotriazol-1-ol (0.061 g), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (0.087 g) and 2.0 mol/L solution of N-methylamine in THF (0.25 ml), and the mixture was stirred at room temperature for 15 hr. Saturated aqueous sodium hydrogencarbonate solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methanol), and recrystallized from ethyl acetate-hexane to give the title compound (0.150 g, yield 67%) as colorless crystals.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (methanol)
  6. customrecrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-30d3884e5ece4194933f96d0b39ac6bc
Source dataset
uspto-grants-2010_01
Patent number
US07652133B2

Reaction notes

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