Dimethylamine → 3-(5-Dimethylaminomethyl-2-methyl-pyrazolo[1,5-a]pyridin-3-yl)-4-(7-methyl-1H-indol-3-yl)-pyrrole-2,5-dione

HRID 402871Notes

Reaction equation

HRID 402871 reaction equation
[CH3:1][NH:2][CH3:3].[CH3:4][C:5]1[C:19]([C:20]2[C:21](=[O:36])[NH:22][C:23](=[O:35])[C:24]=2[C:25]2[C:33]3[C:28](=[C:29]([CH3:34])[CH:30]=[CH:31][CH:32]=3)[NH:27][CH:26]=2)=[C:8]2[CH:9]=[C:10]([CH2:13]OS(C)(=O)=O)[CH:11]=[CH:12][N:7]2[N:6]=1>>[CH3:1][N:2]([CH2:13][C:10]1[CH:11]=[CH:12][N:7]2[N:6]=[C:5]([CH3:4])[C:19]([C:20]3[C:21](=[O:36])[NH:22][C:23](=[O:35])[C:24]=3[C:25]3[C:33]4[C:28](=[C:29]([CH3:34])[CH:30]=[CH:31][CH:32]=4)[NH:27][CH:26]=3)=[C:8]2[CH:9]=1)[CH3:3]

Participants

3

Reactant 2

HCID 674DimethylamineHCID 59192039methanesulfonic acid 2-methyl-3-[4-(7-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-pyrazolo[1,5-a]pyridin-5-ylmethyl ester

Product 1

HCID 249675193-(5-Dimethylaminomethyl-2-methyl-pyrazolo[1,5-a]pyridin-3-yl)-4-(7-methyl-1H-indol-3-yl)-pyrrole-2,5-dioneYield 62.6%

Procedure

Dimethylamine (approx. 50% solution in DMF, 0.04 ml, 0.27 mmol, 2.0 equiv) is added at room temperature under an atmosphere of argon to a solution of methanesulfonic acid 2-methyl-3-[4-(7-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-pyrazolo[1,5-a]pyridin-5-ylmethyl ester (80 mg, 0.17 mmol). The reaction mixture is stirred at room temperature for 20 minutes. After dilution with water, the mixture is extracted three times with EtOAc. The combined organic layers are washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification via flash chromatography (CH2Cl2/MeOH 95:5) affords the title compound (44 mg, 62%). 1H NMR (400 MHz, d6-DMSO): δ=11.77 (s, 1H), 10.93 (s, 1H), 8.48 (d, J=6.9 Hz, 1H), 7.94 (d, J=3.0 Hz, 1H), 6.79 (br s, 1H), 6.74 (d, J=7.1 Hz, 1H), 6.65 (dd, J=7.1/1.7 Hz, 1H), 6.45 (t, J=7.1 Hz, 1H), 6.11 (d, J=8.1 Hz, 1H), 4.10 (q, J=5.4 Hz, 2H), 3.18 (s, 3H), 3.17 (s, 3H), 2.39 (s, 3H), 2.20 (s, 3H). MS (ES+): 414 (M+H)+.

Workup

  1. extractionAfter dilution with water, the mixture is extracted three times with EtOAc
  2. washThe combined organic layers are washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification via flash chromatography (CH2Cl2/MeOH 95:5)

Sources & evidence

ORD record
ord-3aef526d01634ccbb1d34dedd4f3a3e8
Source dataset
uspto-grants-2014_06
Patent number
US08742132B2

Reaction notes

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