Pyridine → 2,6-Difluoro-N-(8-(4-fluorobenzenesulfonyl)-5,6,7,8-tetrahydro[1,8]naphthyridin-2-yl)benzamide

HRID 1054910Notes

Reaction equation

HRID 1054910 reaction equation
[F:1][C:2]1[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:3]=1[C:4]([NH:6][C:7]1[CH:16]=[CH:15][C:14]2[CH2:13][CH2:12][CH2:11][NH:10][C:9]=2[N:8]=1)=[O:5].N1C=CC=CC=1.[F:28][C:29]1[CH:34]=[CH:33][C:32]([S:35](Cl)(=[O:37])=[O:36])=[CH:31][CH:30]=1>ClCCl>[F:1][C:2]1[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:3]=1[C:4]([NH:6][C:7]1[CH:16]=[CH:15][C:14]2[CH2:13][CH2:12][CH2:11][N:10]([S:35]([C:32]3[CH:33]=[CH:34][C:29]([F:28])=[CH:30][CH:31]=3)(=[O:37])=[O:36])[C:9]=2[N:8]=1)=[O:5]

Participants

5

Reactant 3

HCID 1049PyridineHCID 95884-Fluorobenzenesulfonyl chlorideHCID 900116482,6-difluoro-N-(5,6,7,8-tetrahydro[1,8]naphthyridin-2-yl)benzamide

Product 1

HCID 725439832,6-Difluoro-N-(8-(4-fluorobenzenesulfonyl)-5,6,7,8-tetrahydro[1,8]naphthyridin-2-yl)benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2,6-Difluoro-N-(5,6,7,8-tetrahydro[1,8]naphthyridin-2-yl)benzamide (30 mg, 0.10 mmol) was dissolved in dichloromethane (0.3 mL) and pyridine (0.025 mL, 0.31 mmol). 4-Fluorobenzenesulfonyl chloride (23 mg, 0.12 mmol) was then added and the reaction mixture was stirred at room temperature for 12 hours. Next, the reaction mixture was washed with 1M HCl(aq), sat'd NaHCO3(aq), and brine. The resulting organic solution was concentrated, dissolved in DMSO, and purified by HPLC to give 2,6-difluoro-N-(8-(4-fluorobenzenesulfonyl)-5,6,7,8-tetrahydro[1,8]naphthyridin-2-yl]benzamide. 1H NMR 250 MHz CDCl3 δ 8.13 (bs, 1H), 8.03 (dd, J=7.9, 4.3 Hz, 2H), 7.83 (d, J=7.9 Hz, 1H), 7.48 (p, J=6.5 Hz, 1H), 7.38 (d, J=7.9 Hz, 1H), 7.15 (t, J=7.9 Hz, 2H), 7.06 (t, J=7.8 Hz, 2H), 4.07 (dd, J=5.8, 4.3 Hz, 2H), 2.76 (t, J=6.5 Hz, 2H), 2.06 (p, J=5.8 Hz, 2H). LCMS (ESI): calc. C21H16F3N3O3S=447; obs. M+H=448.

Workup

  1. washNext, the reaction mixture was washed with 1M HCl(aq), sat'd NaHCO3(aq), and brine
  2. concentrationThe resulting organic solution was concentrated
  3. dissolutiondissolved in DMSO
  4. custompurified by HPLC

Sources & evidence

ORD record
ord-3a8b589f3bc4413eb31bee6f4b574dfe
Source dataset
uspto-grants-2016_07
Patent number
US09394315B2

Reaction notes

Loading…