4-Chloroaniline → HCID 89784513, compound

HRID 1055851Notes

Reaction equation

HRID 1055851 reaction equation
[Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.Cl[C:10]1[CH:19]=[CH:18][C:17]2[C:12](=[C:13]([C:20]3[NH:28][C:27]4[CH2:26][CH2:25][NH:24][C:23](=[O:29])[C:22]=4[CH:21]=3)[CH:14]=[CH:15][CH:16]=2)[N:11]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>>[Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[C:13]([C:20]4[NH:28][C:27]5[CH2:26][CH2:25][NH:24][C:23](=[O:29])[C:22]=5[CH:21]=4)[CH:14]=[CH:15][CH:16]=3)[N:11]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 78124-ChloroanilineHCID 2733832Lithium HexamethyldisilazideHCID 897835482-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 89784513HCID 89784513, compoundYield 17.5%

Procedure

To 4-chloroaniline (Alfa Aesar, Ward Hill, Mass.; 0.225 g, 1.763 mmol) and 2-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 1; 0.075 g, 0.252 mmol) was added LHMDS (1.0 M solution in THF; 1.763 ml, 1.763 mmol). After 3 h, the reaction mixture 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. EtOAc was added, the layers were separated, and the organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The solid was suspended in MeOH and filtered, rinsing 1× MeOH to give 2-(2-((4-chlorophenyl)amino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.017 g, 0.044 mmol, 17% yield) as a dull-yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.96 (1H, br. s), 9.62 (1H, s), 8.12 (1H, d, J=9.0 Hz), 7.89 (1H, dt, J=7.2, 0.8 Hz), 7.72-7.81 (2H, m), 7.61 (1H, dt, J=7.8, 0.9 Hz), 7.36-7.46 (2H, m), 7.31 (1H, t, J=7.6 Hz), 7.08 (1H, d, J=9.0 Hz), 6.88-7.00 (2H, m), 3.37-3.52 (2H, m), 2.70 (2H, t, J=6.9 Hz). m/z (ESI, +ve) 389.0 (M+H)+.

Workup

  1. customthe reaction mixture was partitioned between saturated aq. NH4Cl and DCM
  2. extractionThe aq. layer was extracted with DCM (3×)
  3. dry with materialthe combined organics were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. additionEtOAc was added
  7. customthe layers were separated
  8. dry with materialthe organic layer was dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. filtrationfiltered
  12. washrinsing 1× MeOH

Sources & evidence

ORD record
ord-735e424adf2444a08558ff5fe3f0cb28
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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