Aniline → 2-(2-(phenylamino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

HRID 1055840Notes

Reaction equation

HRID 1055840 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:9]1[CH:18]=[CH:17][C:16]2[C:11](=[C:12]([C:19]3[NH:27][C:26]4[CH2:25][CH2:24][NH:23][C:22](=[O:28])[C:21]=4[CH:20]=3)[CH:13]=[CH:14][CH:15]=2)[N:10]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>>[C:2]1([NH:1][C:9]2[CH:18]=[CH:17][C:16]3[C:11](=[C:12]([C:19]4[NH:27][C:26]5[CH2:25][CH2:24][NH:23][C:22](=[O:28])[C:21]=5[CH:20]=4)[CH:13]=[CH:14][CH:15]=3)[N:10]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 6115AnilineHCID 2733832Lithium HexamethyldisilazideHCID 897835482-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 897839482-(2-(phenylamino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-oneYield 59%

Procedure

A dark red mixture of aniline (0.077 ml, 0.840 mmol), 2-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 1; 0.050 g, 0.168 mmol) and LHMDS (1.0 M solution in THF; 0.840 ml, 0.840 mmol) was sealed and stirred at RT for 1 h. The reaction was then 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. The resulting material was suspended in 1 mL MeOH, sonicated for 1 min, filtered, and rinsed 2× MeOH. The solid was dried in vacuo to give 2-(2-(phenylamino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.035 g, 0.099 mmol, 59% yield) as a light-yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 12.18 (1H, br. s), 9.52 (1H, s), 8.11 (1H, d, J=9.0 Hz), 7.94 (1H, dd, J=7.4, 1.6 Hz), 7.62-7.70 (2H, m), 7.55-7.61 (1H, m), 7.36-7.45 (2H, m), 7.28 (1H, t, J=7.7 Hz), 7.04-7.14 (2H, m), 6.87-6.95 (2H, m), 3.35-3.44 (2H, m), 2.59-2.69 (2H, m). m/z (ESI, +ve) 355.0 (M+H)+.

Workup

  1. customwas sealed
  2. customThe reaction was then partitioned between saturated aq. NH4Cl and DCM
  3. extractionThe aq. layer was extracted with DCM (3×)
  4. dry with materialthe combined organics were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customsonicated for 1 min
  8. filtrationfiltered
  9. washrinsed 2× MeOH
  10. customThe solid was dried in vacuo

Sources & evidence

ORD record
ord-bae7cdf5f6ac4a249536817fc06f69cd
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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