Dimethylamine → 7-Bromo-N,N-dimethyl-1,6-naphthyridine-2-carboxamide

HRID 523075Notes

Reaction equation

[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C:12]([OH:14])=O)=[N:9]2)=[CH:4][N:3]=1.[CH2:15]([N:17](CC)[CH2:18]C)C.ClC(OCC)=O.CNC>CC(C)=O.C1(C)C=CC=CC=1.C(O)C>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([C:12]([N:17]([CH3:18])[CH3:15])=[O:14])=[N:9]2)=[CH:4][N:3]=1

Participants

Conditions

Temperature: 2.5 °C

Procedure

7-Bromo-1,6-naphthyridine-2-carboxylic acid (Preparation 64, 232 mg 0.92 mmole) was azeotroped with ethanol (10 mL) and then with toluene (2×12 mL). The residue was dissolved in acetone (3 mL) with triethylamine (260 uL, 1.85 mmole) and cooled in ice. Ethyl chloroformate (195 uL, 2.03 mmole) was added and the reaction stirred at 0-5° C. for 25 minutes. Dimethylamine (2M in THF, 2.2 mL, 4.4 mmole) was added and the reaction stirred at 0-5° C. for 10 minutes followed by room temperature for 50 minutes. The acetone was evaporated and the residue partitioned between ethyl acetate (25 mL) and water (8 mL). The organic layer was washed with water (8 mL), brine, dried over sodium sulphate and concentrated in vacuo. The residue was purified using preparative TLC eluting with 9:1 ethyl acetate:acetone to afford the title compound (106 mg, 41%).

Workup

temperaturecooled in ice
stirringthe reaction stirred at 0-5° C. for 10 minutes
waitfollowed by room temperature for 50 minutes
customThe acetone was evaporated
customthe residue partitioned between ethyl acetate (25 mL) and water (8 mL)
washThe organic layer was washed with water (8 mL), brine
dry with materialdried over sodium sulphate
concentrationconcentrated in vacuo
customThe residue was purified
washeluting with 9:1 ethyl acetate

Sources & evidence

ORD record: ord-d883f4b4f4584bfd889a8b649a3a1c3a
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09334286B2

Reaction notes

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