Aniline → HCID 89784140, compound

HRID 1055859Notes

Reaction equation

HRID 1055859 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[C:5]([C:12]3[NH:20][C:19]4[CH:18]([CH2:21][CH3:22])[CH2:17][NH:16][C:15](=[O:23])[C:14]=4[CH:13]=3)[CH:6]=[CH:7][CH:8]=2)[N:3]=1.[NH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.C(O)(C(F)(F)F)=O>>[CH2:21]([CH:18]1[CH2:17][NH:16][C:15](=[O:23])[C:14]2[CH:13]=[C:12]([C:5]3[CH:6]=[CH:7][CH:8]=[C:9]4[C:4]=3[N:3]=[C:2]([NH:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:11]=[CH:10]4)[NH:20][C:19]1=2)[CH3:22]

Participants

5

Reactant 4

HCID 6115AnilineHCID 6422Trifluoroacetic acidHCID 2733832Lithium HexamethyldisilazideHCID 89783190HCID 89783190, compound

Product 1

HCID 89784140HCID 89784140, compoundYield 23.9%

Procedure

A mixture of 2-(2-chloroquinolin-8-yl)-7-ethyl-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 22; 0.075 g, 0.230 mmol) and aniline (0.105 ml, 1.151 mmol) was treated with LHMDS (1.0 M in THF; 1.151 ml, 1.151 mmol) at RT. After 2 h, the reaction was concentrated, then dissolved in DMSO and treated with TFA (0.089 ml, 1.151 mmol). This material was purified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 10-70% 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 rac-7-ethyl-2-(2-(phenylamino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.021 g, 0.055 mmol, 23.85% yield): 1H NMR (400 MHz, DMSO-d6) δ ppm 12.24 (1H, br. s), 9.53 (1H, s), 8.12 (1H, d, J=9.0 Hz), 7.96 (1H, dt, J=7.5, 0.6 Hz), 7.53-7.67 (3H, m), 7.39 (2H, t, J=7.8 Hz), 7.29 (1H, t, J=7.6 Hz), 7.03-7.15 (2H, m), 6.86-6.95 (2H, m), 3.46-3.61 (1H, m), 3.06-3.21 (1H, m), 2.58-2.71 (1H, m), 1.15-1.32 (2H, m), 0.66 (3H, t, J=7.3 Hz). m/z (ESI, +ve) 383.0 (M+H)+. A portion of this material was resolved by chiral SFC (Chiralpak IC (21×250 mm, 5 μm); additive in supercritical fluid CO2 was 50% MeOH with 20 mM NH3; 60 mL/min; column temperature 40° C.; outlet pressure 100 bar) to give separated enantiomers (R)-7-ethyl-2-(2-(phenylamino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 25) and (S)-7-ethyl-2-(2-(phenylamino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one. (Example 26).

Workup

  1. concentrationthe reaction was concentrated
  2. dissolutiondissolved in DMSO
  3. customThis material was purified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 10-70% ACN/H2O with 0.1% TFA)
  4. additionproduct-containing fractions were treated with saturated aq. NaHCO3 and DCM
  5. customThe organic layer was separated
  6. extractionthe aq. layer was extracted 3×DCM
  7. dry with materialThe combined organic layers were then dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ee90b80a7685433484285c41d24ad5fc
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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