Thionyl Chloride → 6-(5-chloromethyl-pyridin-3-yl)-1-methyl-3,4-dihydro-1H-[1,5]naphthyridin-2-one

HRID 1774799Notes

Reaction equation

HRID 1774799 reaction equation
O[CH2:2][C:3]1[CH:4]=[C:5]([C:9]2[N:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]([CH3:19])[C:14](=[O:20])[CH2:13][CH2:12]3)[CH:6]=[N:7][CH:8]=1.S(Cl)([Cl:23])=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Cl:23][CH2:2][C:3]1[CH:4]=[C:5]([C:9]2[N:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]([CH3:19])[C:14](=[O:20])[CH2:13][CH2:12]3)[CH:6]=[N:7][CH:8]=1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 866791626-(5-hydroxymethyl-pyridin-3-yl)-1-methyl-3,4-dihydro-1H-[1,5]naphthyridin-2-one

Product 1

HCID 866791636-(5-chloromethyl-pyridin-3-yl)-1-methyl-3,4-dihydro-1H-[1,5]naphthyridin-2-oneYield 86.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
3.5 °C

Procedure

At 0° C., 6-(5-hydroxymethyl-pyridin-3-yl)-1-methyl-3,4-dihydro-1H-[1,5]naphthyridin-2-one (170 mg, 0.63 mmol) in DCM (15 mL) was treated with thionyl chloride (0.32 mL, 4.0 mmol). After the addition, the reaction mixture was allowed to stir at 2-5° C. for 2 hours before it was poured into satd. aq. NaHCO3 solution (50 mL). After extraction with EtOAc, the organic layer was washed with brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo to give 6-(5-chloromethyl-pyridin-3-yl)-1-methyl-3,4-dihydro-1H-[1,5]naphthyridin-2-one (156 mg, 86.3%) as yellow oil. MS: 288.1 (M+H+).

Workup

  1. additionAfter the addition
  2. additionwas poured into satd
  3. extractionAfter extraction with EtOAc
  4. washthe organic layer was washed with brine
  5. customdried over anhy
  6. filtrationNa2SO4, filtered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-aa68d75ea71a4cbd9ea5fec5c379ad1e
Source dataset
uspto-grants-2016_02
Patent number
US09260408B2

Reaction notes

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