4-Chlorophenol → HCID 89783562, compound

HRID 1055854Notes

Reaction equation

HRID 1055854 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.Cl[C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[C:15]([C:22]3[NH:30][C:29]4[CH2:28][CH2:27][NH:26][C:25](=[O:31])[C:24]=4[CH:23]=3)[CH:16]=[CH:17][CH:18]=2)[N:13]=1.C(O)(C(F)(F)F)=O>CN(C=O)C.CS(C)=O>[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][C:12]2[CH:21]=[CH:20][C:19]3[C:14](=[C:15]([C:22]4[NH:30][C:29]5[CH2:28][CH2:27][NH:26][C:25](=[O:31])[C:24]=5[CH:23]=4)[CH:16]=[CH:17][CH:18]=3)[N:13]=2)=[CH:6][CH:5]=1

Participants

7

Reactant 4

HCID 46844-ChlorophenolHCID 6422Trifluoroacetic acidHCID 24758Sodium hydrideHCID 897835482-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 89783562HCID 89783562, compoundYield 45%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

NaH (60% in mineral oil; 0.071 g, 1.763 mmol) was suspended in 1 mL DMF and p-chlorophenol (Aldrich; 0.174 ml, 1.763 mmol) was added. After 10 min, 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, and the reaction was sealed and heated at 70° C. for 2 h, then at 90° C. for 1 h. The reaction mixture was then treated with TFA (0.136 ml, 1.763 mmol) and 1 mL DMSO, filtered, and purified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 20-100% ACN/H2O with 0.1% TFA); product-containing fractions were concentrated in vacuo to give 2-(2-(4-chlorophenoxy)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.044 g, 0.113 mmol, 45% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.07 (1H, br. s), 8.50 (1H, d, J=9.0 Hz), 8.11 (1H, dt, J=7.6, 0.7 Hz), 7.80 (1H, dt, J=7.9, 0.7 Hz), 7.60-7.71 (2H, m), 7.31-7.55 (4H, m), 6.94 (2H, dd, J=2.0, 0.4 Hz), 3.31-3.42 (2H, m), 2.47-2.51 (2H, m). m/z (ESI, +ve) 389.9 (M+H)+.

Workup

  1. customthe reaction was sealed
  2. waitat 90° C. for 1 h
  3. filtrationfiltered
  4. custompurified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 20-100% ACN/H2O with 0.1% TFA)
  5. concentrationproduct-containing fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-37f4ac3af2c149dd8f5d798bcb21b996
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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