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 216651Notes

Reaction equation

HRID 216651 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=6.9Hz, 1H), 7.94 (d, J=3.0 Hz, 1H), 6.79 (br s, 1H), 6.74 (d=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-0aedb969cc5b471285628b9bf141d1cb
Source dataset
uspto-grants-2012_06
Patent number
US08193236B2

Reaction notes

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