Methanesulfonyl chloride → 2-{7-[(3,4-Difluorophenyl)methoxy]-1,5-naphthyridin-3-yl}acetonitrile

HRID 513963Notes

Reaction equation

HRID 513963 reaction equation
CS(O[CH2:6][C:7]1[CH:8]=[N:9][C:10]2[C:15]([CH:16]=1)=[N:14][CH:13]=[C:12]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22]([F:25])=[C:21]([F:26])[CH:20]=1)[CH:11]=2)(=O)=O.FC1C=C(C=CC=1F)COC1C=C2C(C=C(CO)C=N2)=[N:35][CH:34]=1.CS(Cl)(=O)=O>C(Cl)Cl>[F:26][C:21]1[CH:20]=[C:19]([CH2:18][O:17][C:12]2[CH:11]=[C:10]3[C:15]([CH:16]=[C:7]([CH2:6][C:34]#[N:35])[CH:8]=[N:9]3)=[N:14][CH:13]=2)[CH:24]=[CH:23][C:22]=1[F:25]

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 86301659(7-((3,4-Difluorobenzyl)oxy)-1,5-naphthyridin-3-yl)methanolHCID 90418375(7-((3,4-Difluorobenzyl)oxy)-1,5-naphthyridin-3-yl)methyl methanesulfonate

Product 1

HCID 863016602-{7-[(3,4-Difluorophenyl)methoxy]-1,5-naphthyridin-3-yl}acetonitrileYield 64%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(7-((3,4-difluorobenzyl)oxy)-1,5-naphthyridin-3-yl)methyl methanesulfonate. To a solution of (7-((3,4-difluorobenzyl)oxy)-1,5-naphthyridin-3-yl)methanol (Example 73, 90 mg, 0.3 mmol) in DCM (4 mL) was added methanesulfonyl chloride (0.05 mL, 0.61 mmol) followed by TEA (0.06 mL, 0.43 mmol). The reaction mixture was stirred at RT for 1 h and quenched with saturated NaHCO3 solution. The mixture was extracted with DCM (2×) and the combined organic layers were dried, filtered and concentrated under reduced pressure. Purification (FCC, SiO2, 0-80%, EtOAc/hexanes) afforded the title compound as a white solid (73 mg, 64%). [M+H]=381.1.

Workup

  1. customquenched with saturated NaHCO3 solution
  2. extractionThe mixture was extracted with DCM (2×)
  3. customthe combined organic layers were dried
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification (FCC, SiO2, 0-80%, EtOAc/hexanes)

Sources & evidence

ORD record
ord-a99bad42efcb4236a01f49892c1855d7
Source dataset
uspto-grants-2015_08
Patent number
US09102674B2

Reaction notes

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