Ammonium Chloride → 3-(7-Methyl-1H-indol-3-yl)-4-[5-(4-methyl-piperazin-1-yl)-pyridin-3-yl]-pyrrole-2,5-dione

HRID 1992634Notes

Reaction equation

HRID 1992634 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[C:10]([CH2:14][C:15]([NH2:17])=[O:16])[CH:11]=[N:12][CH:13]=2)[CH2:4][CH2:3]1.C[O:19][C:20](=O)[C:21]([C:23]1[C:31]2[C:26](=[C:27]([CH3:32])[CH:28]=[CH:29][CH:30]=2)[NH:25][CH:24]=1)=O.CC([O-])(C)C.[K+].[NH4+].[Cl-]>CN(C=O)C.C1COCC1.CCOC(C)=O>[CH3:32][C:27]1[CH:28]=[CH:29][CH:30]=[C:31]2[C:26]=1[NH:25][CH:24]=[C:23]2[C:21]1[C:20](=[O:19])[NH:17][C:15](=[O:16])[C:14]=1[C:10]1[CH:11]=[N:12][CH:13]=[C:8]([N:5]2[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]2)[CH:9]=1

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 11241405Methyl 7-methyl-alpha-oxo-1H-indole-3-acetateHCID 23665647Potassium tert-butoxideHCID 668692842-[5-(4-Methyl-piperazin-1-yl)-pyridin-3-yl]-acetamide

Product 1

HCID 115675473-(7-Methyl-1H-indol-3-yl)-4-[5-(4-methyl-piperazin-1-yl)-pyridin-3-yl]-pyrrole-2,5-dione

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

2-[5-(4-Methyl-piperazin-1-yl)-pyridin-3-yl]-acetamide (150 mg, 0.64 mmol) and (7-methyl-1H-indol-3-yl)-oxo-acetic acid methyl ester (209 mg, 0.96 mmol) are dissolved under an atmosphere of argon in a mixture of dry DMF (2 ml) and dry THF (2 ml). A solution of 1.0 M KOtBu in THF (1.9 ml, 1.9 mmol) is then added at RT. After 1 h at 50° C., TLC analysis indicated complete conversion of starting materials. The reaction mixture is diluted with EtOAc and poured into a saturated aqueous NH4Cl solution. The organic layer is separated, washed with brine, dried over Na2SO4, and the organic solvent is evaporated. The residue is purified by FCC (EtOAc/AcOH/H2O 600:115:150) to afford the title compound. 1H NMR (d6-DMSO 400 MHz): δ 2.15 (s, 3H), 2.28-2.32 (m, 2H), 2.92-3.00 (m, 2H), 3.15 (s, 3H), 6.21 (d, J=9 Hz, 1H), 6.64 (t, J=9 Hz, 1H), 6.88 (d, J=9 Hz, 1H), 7.22 (s, 1H), 7.98 (br s, 1H), 8.20-8.22 (m, 1H). ES+−MS: 402.6 [M+H]+.

Workup

  1. customThe organic layer is separated
  2. washwashed with brine
  3. dry with materialdried over Na2SO4
  4. customthe organic solvent is evaporated
  5. customThe residue is purified by FCC (EtOAc/AcOH/H2O 600:115:150)

Sources & evidence

ORD record
ord-64772c9654fe44949b8cecccb25e2407
Source dataset
uspto-grants-2010_01
Patent number
US07648989B2

Reaction notes

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