Benzoyl chloride → N-(1-Benzoyl-8-chloro-6-cyano-1,2,3,4-tetrahydroquinolin-3-yl)-benzenesulfonamide

HRID 1643898Notes

Reaction equation

HRID 1643898 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:22]#[N:23])[CH:5]=[C:6]2[C:11]=1[NH:10][CH2:9][CH:8]([NH:12][S:13]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)(=[O:15])=[O:14])[CH2:7]2.[C:24](Cl)(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>N1C=CC=CC=1.C(Cl)Cl>[C:24]([N:10]1[C:11]2[C:6](=[CH:5][C:4]([C:22]#[N:23])=[CH:3][C:2]=2[Cl:1])[CH2:7][CH:8]([NH:12][S:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)(=[O:15])=[O:14])[CH2:9]1)(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

5

Reactant 2

HCID 7412Benzoyl chlorideHCID 66757150N-(8-chloro-6-cyano-1,2,3,4-tetrahydroquinolin-3-yl)-benzene-sulfonamide

Product 1

HCID 66757534N-(1-Benzoyl-8-chloro-6-cyano-1,2,3,4-tetrahydroquinolin-3-yl)-benzenesulfonamideYield 28.1%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of compound 163A (164 mg, 0.472 mmol) in pyridine (1 mL) and CH2Cl2 (1 mL) at RT was added benzoyl chloride (82 μL, 0.71 mmol), and the mixture was then stirred at 50° C. for 16 h. After cooling to RT, the reaction was concentrated in vacuo and the resultant residue was taken into MeOH (4 mL), and Et3N (1 mL) added. The reaction was stirred at 70° C. for 1 h. After cooling to RT, the reaction was concentrated. The residue was diluted with 10% aqueous citric acid, then extracted with EtOAc (3×15 mL). The combined EtOAc extracts were concentrated. The resulting residue was purified using preparative HPLC (YMC S5 ODS 20×100 mm) eluting with MeOH (50-80%) in H2O for 8 min, and then 80% MeOH in H2O for 7 min to give the title compound (60 mg, 28%) as a white solid. HPLC: 99% at 6.2 min (retention time) (Conditions: Zorbax SB C18 (4.6×75 mm); Eluted with 0% to 100% B, 8 min gradient. (A=90% H2O−10% MeOH−0.1% H3PO4 and B=10% H2O−90% MeOH−0.1% H3PO4); Flow rate at 2.5 mL/min. UV detection at 220 nm). MS (ES): m/z 452 [M+H]+.

Workup

  1. temperatureAfter cooling to RT
  2. concentrationthe reaction was concentrated in vacuo
  3. additionadded
  4. stirringThe reaction was stirred at 70° C. for 1 h
  5. temperatureAfter cooling to RT
  6. concentrationthe reaction was concentrated
  7. additionThe residue was diluted with 10% aqueous citric acid
  8. extractionextracted with EtOAc (3×15 mL)
  9. concentrationThe combined EtOAc extracts were concentrated
  10. customThe resulting residue was purified
  11. washeluting with MeOH (50-80%) in H2O for 8 min

Sources & evidence

ORD record
ord-f67b402873744d0786c393d7fa02b6e3
Source dataset
uspto-grants-2012_02
Patent number
US08119808B2

Reaction notes

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