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

HRID 1055842Notes

Reaction equation

HRID 1055842 reaction equation
[H-].[Na+].[C:3]1([SH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.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.CO>CN1C(=O)CCC1>[C:3]1([S:9][C:11]2[CH:20]=[CH:19][C:18]3[C:13](=[C:14]([C:21]4[NH:29][C:28]5[CH2:27][CH2:26][NH:25][C:24](=[O:30])[C:23]=5[CH:22]=4)[CH:15]=[CH:16][CH:17]=3)[N:12]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 7969ThiophenolHCID 24758Sodium hydrideHCID 897835482-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 897836832-(2-(phenylthio)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-oneYield 45%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
70 °C

Procedure

To NaH (60 wt % in mineral oil; 0.050 g, 1.259 mmol) in 1 mL NMP was added benzenethiol (0.129 ml, 1.259 mmol). After 10 min, a clear/colorless solution resulted. 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 as a solid and the reaction became orange. After 1 h, the reaction was sealed and heated to 70° C. for 1 h. The reaction was cooled and was partitioned between saturated aq. NaHCO3 and EtOAc. The organic layer was washed with saturated aq. NaHCO3 (3×) and saturated aq. NaCl (1×), and the organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The material was treated with DCM and purified by silica gel chromatography (25 g column) using 0-50% 90/10 DCM/MeOH in DCM. The product-containing fractions were concentrated to afford a yellow solid. The material was treated with 1 mL MeOH, sonicated, and filtered, rinsing with MeOH, to give 2-(2-(phenylthio)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.042 g, 0.113 mmol, 45% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.18-11.45 (1H, m), 8.28 (1H, d, J=8.6 Hz), 8.09 (1H, dd, J=7.5, 1.5 Hz), 7.67-7.79 (3H, m), 7.48-7.61 (4H, m), 7.36 (1H, d, J=8.8 Hz), 7.05 (1H, d, J=2.3 Hz), 6.92-6.98 (1H, m), 3.33-3.42 (2H, m), 2.50-2.55 (2H, m). m/z (ESI, +ve) 371.9 (M+H)+.

Workup

  1. customa clear/colorless solution resulted
  2. waitAfter 1 h
  3. customthe reaction was sealed
  4. temperatureThe reaction was cooled
  5. customwas partitioned between saturated aq. NaHCO3 and EtOAc
  6. washThe organic layer was washed with saturated aq. NaHCO3 (3×) and saturated aq. NaCl (1×)
  7. dry with materialthe organics were dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. additionThe material was treated with DCM
  11. custompurified by silica gel chromatography (25 g column)
  12. concentrationThe product-containing fractions were concentrated
  13. customto afford a yellow solid
  14. customsonicated
  15. filtrationfiltered
  16. washrinsing with MeOH

Sources & evidence

ORD record
ord-2e2ebff8bd454123b1d1c4f87ca9faf8
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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