N-Ethylaniline → HCID 89783659, compound

HRID 1055850Notes

Reaction equation

HRID 1055850 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH2:11]([NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH3:12].Cl[C:21]1[CH:30]=[CH:29][C:28]2[C:23](=[C:24]([C:31]3[NH:39][C:38]4[CH2:37][CH2:36][NH:35][C:34](=[O:40])[C:33]=4[CH:32]=3)[CH:25]=[CH:26][CH:27]=2)[N:22]=1>>[CH2:11]([N:13]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:21]1[CH:30]=[CH:29][C:28]2[C:23](=[C:24]([C:31]3[NH:39][C:38]4[CH2:37][CH2:36][NH:35][C:34](=[O:40])[C:33]=4[CH:32]=3)[CH:25]=[CH:26][CH:27]=2)[N:22]=1)[CH3:12]

Participants

4

Reactant 3

HCID 7670N-EthylanilineHCID 2724254Sodium bis(trimethylsilyl)amideHCID 897835482-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 89783659HCID 89783659, compoundYield 40.8%

Procedure

NaHMDS (1.0 M solution in THF; 1.975 ml, 1.975 mmol) was added to N-ethylaniline (0.249 ml, 1.975 mmol) and 2-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 1; 0.084 g, 0.282 mmol). The dark red reaction was stirred rapidly at RT. After 2 h, the reaction was quenched with saturated aq. NH4Cl. The reaction was partitioned between saturated aq. NH4Cl and DCM. The aq. layer was extracted with DCM (3×), and the combined organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. This material was dissolved in DMSO and purified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 10-80% ACN/H2O with 0.1% TFA); product-containing fractions were treated with saturated aq. NaHCO3 and DCM. The combined organic layers were then the aq. layer was extracted 3×DCM, the combined organics layers were then dried over Na2SO4, filtered, and concentrated in vacuo to give 2-(2-(ethyl(phenyl)amino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.044 g, 0.115 mmol, 40.8% yield) as an orange solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 12.07-12.29 (1H, m), 7.92-8.19 (2H, m), 7.48-7.63 (3H, m), 7.34-7.47 (3H, m), 7.26 (1H, t, J=7.6 Hz), 6.98-7.07 (1H, m), 6.89-6.98 (1H, m), 6.83 (1H, d, J=9.2 Hz), 4.08 (2H, q, J=7.0 Hz), 3.36-3.44 (2H, m), 2.69 (2H, t, J=6.9 Hz), 1.30 (3H, t, J=7.0 Hz). m/z (ESI, +ve) 383.0 (M+H)+.

Workup

  1. customThe dark red reaction
  2. customthe reaction was quenched with saturated aq. NH4Cl
  3. customThe reaction was partitioned between saturated aq. NH4Cl and DCM
  4. extractionThe aq. layer was extracted with DCM (3×)
  5. dry with materialthe combined organics were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThis material was dissolved in DMSO
  9. custompurified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 10-80% ACN/H2O with 0.1% TFA)
  10. additionproduct-containing fractions were treated with saturated aq. NaHCO3 and DCM
  11. extractionthe aq. layer was extracted 3×DCM
  12. dry with materialthe combined organics layers were then dried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1d9b40826b4a4e049c68796e6a14d6f2
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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