Trifluoroacetic acid → HCID 89783772, compound

HRID 1055862Notes

Reaction equation

HRID 1055862 reaction equation
[CH2:1]([NH:3][C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1)[CH3:2].Cl[C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[C:14]([C:21]3[NH:29][C:28]4[CH2:27][CH2:26][NH:25][C:24](=[O:30])[C:23]=4[CH:22]=3)[CH:15]=[CH:16][CH:17]=2)[N:12]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C(O)(C(F)(F)F)=O>C1COCC1.CS(C)=O>[CH2:1]([N:3]([C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1)[C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[C:14]([C:21]3[NH:29][C:28]4[CH2:27][CH2:26][NH:25][C:24](=[O:30])[C:23]=4[CH:22]=3)[CH:15]=[CH:16][CH:17]=2)[N:12]=1)[CH3:2]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 2724254Sodium bis(trimethylsilyl)amide2×HCID 11804744N-ethylpyridin-3-amineHCID 897835482-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 89783772HCID 89783772, compoundYield 11%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of N-ethylpyridin-3-amine (Enamine, Kiev, Ukraine; 0.164 g, 1.343 mmol) and 2-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 1; 0.080 g, 0.269 mmol) was added NaHMDS (1.0 M in THF; 1.343 ml, 1.343 mmol). The dark red reaction was stirred for 30 min, then 0.5 mL 1.0 M NaHMDS in THF was added. After 30 min, the reaction was concentrated in vacuo and 2.5 mL DMSO and TFA (0.207 ml, 2.69 mmol) were added. Purified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 5-60% ACN/H2O with 0.1% TFA); product-containing fractions were treated with saturated aq. NaHCO3 and DCM. The organic layer was separated, and the aq. layer was extracted 3×DCM. The combined organic layers were then dried over Na2SO4, filtered, and concentrated in vacuo to give 2-(2-(ethyl(pyridin-3-yl)amino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.011 g, 0.029 mmol, 11% yield) as a solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.97 (1H, br. s), 8.63-8.69 (1H, m), 8.55-8.62 (1H, m), 8.08 (1H, d, J=9.2 Hz), 7.99 (1H, dt, J=7.5, 0.7 Hz), 7.88 (1H, dt, J=8.2, 2.1 Hz), 7.53-7.63 (2H, m), 7.29 (1H, t, J=7.6 Hz), 6.99-7.07 (1H, m), 6.90-6.97 (2H, m), 4.11 (2H, q, J=7.0 Hz), 3.37-3.45 (2H, m), 2.66 (2H, t, J=6.9 Hz), 1.30 (3H, t, J=7.1 Hz). m/z (ESI, +ve) 384.2 (M+H)+.

Workup

  1. customThe dark red reaction
  2. waitAfter 30 min
  3. additionwere added
  4. customPurified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 5-60% ACN/H2O with 0.1% TFA)
  5. additionproduct-containing fractions were treated with saturated aq. NaHCO3 and DCM
  6. customThe organic layer was separated
  7. extractionthe aq. layer was extracted 3×DCM
  8. dry with materialThe combined organic layers were then dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-88d2da4742ea43f992db3173f3a99c4a
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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