Methylamine → HCID 9813880, compound

HRID 984851Notes

Reaction equation

HRID 984851 reaction equation
[CH3:1][N:2]1[C:14]2[C:13]3[CH:12]=[C:11]4[CH:15]=[CH:16][CH:17]=[CH:18][C:10]4=[CH:9][C:8]=3[N:7]=[C:6](Cl)[C:5]=2[N:4]=[CH:3]1.[CH3:20][NH2:21]>CCOC(C)=O>[CH3:1][N:2]1[C:14]2[C:13]3[CH:12]=[C:11]4[CH:15]=[CH:16][CH:17]=[CH:18][C:10]4=[CH:9][C:8]=3[N:7]=[C:6]([NH:21][CH3:20])[C:5]=2[N:4]=[CH:3]1

Participants

4

Reactant 2

HCID 6329MethylamineHCID 22285039HCID 22285039, compound

Product 1

HCID 9813880HCID 9813880, compoundYield 4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 1-methyl-4-chlorobenzo(g)imidazo(4,5-c)quinoline (Preparation 19 in Example 11) (130 mg, 0.49 mmol) and MeNH2 (2.0M/THF, 1.5 mL, 2.92 mmol) was heated in a pressure tube at 80° C. for 18 hours. After the reaction mixture was cooled to RT, it was diluted with EtOAc (100 mL), washed with sat'd NaCO3 (50 mL), and brine. The organic layer was dried over MgSO4, filtered and evaporated in vacuo. The crude material was submitted to flash chromatography (5% MeOH/EtOAc) affording the title compound as a pale white solid (5.2 mg, 4%). 1H NMR (CDCl3): 8.44 (s, 1H), 8.35 (s, 1H), 7.94 (d, J=8.3, 1H), 7.90 (d, J=8.3, 1H), 7.72 (s, 1H), 7.46 (m, 1H), 7.40 (m, 1H), 5.95 (b, 1H), 4.28 (s, 3H), 3.31 (s, 3H). (ESI) m/z (M+H)+=263.14. Inhibition of IKK-1 activity was measured using the assay of Example 2, where the inhibitory potential of the compound of Example 16 resulted in an IC50 of 0.80 μM.

Workup

  1. temperatureAfter the reaction mixture was cooled to RT
  2. washwashed with sat'd NaCO3 (50 mL), and brine
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. customevaporated in vacuo

Sources & evidence

ORD record
ord-ca5a513ca78845a0bcdadc5a66158457
Source dataset
uspto-grants-2005_03
Patent number
US06869956B2

Reaction notes

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