Sodium Carbonate → 2-(3-Methyl-4-nitrophenyl)-1,2,3,4-tetrahydro-2,7-naphthyridine

HRID 338760Notes

Reaction equation

Cl.Cl.[CH2:3]1[C:12]2[C:7](=[CH:8][CH:9]=[N:10][CH:11]=2)[CH2:6][CH2:5][NH:4]1.F[C:14]1[CH:15]=[CH:16][C:17]([N+:21]([O-:23])=[O:22])=[C:18]([CH3:20])[CH:19]=1.C([O-])([O-])=O.[Na+].[Na+]>CN1C(=O)CCC1>[CH3:20][C:18]1[CH:19]=[C:14]([N:10]2[CH2:9][CH2:8][C:7]3[C:12](=[CH:3][N:4]=[CH:5][CH:6]=3)[CH2:11]2)[CH:15]=[CH:16][C:17]=1[N+:21]([O-:23])=[O:22]

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of commercially available 1,2,3,4-tetrahydro-2,7-naphthyridine dihydrochloride (207 mg, 1.0 mmol), 5-fluoro-2-nitrotoluene (0.244 mL, 2.0 mmol), and Na2CO3 (0.53 g, 5.0 mmol) in 3.0 mL NMP was heated at 110° C. for 2.5 hours. The solids were filtered off and then rinsed with EtOAc. The EtOAc portion was washed with a H2O/brine mixture, H2O, brine, dried with anhydrous Na2SO4, and evaporated to an oil. The oil was chromatographed eluting with CHCl3/EtOAc and the resulting solid triturated with EtOAc/hexane to give the title compound as a yellow solid (123 mg, 45%). 1H NMR (CDCl3) δ: 8.48 (s, 1H), 8.44 (d, J=5.3 Hz, 1H), 8.14 (d, J=9.1 Hz, 1H), 7.15 (d, J=5.0 Hz, 1H), 6.76 (dd, J=9.2, 2.8 Hz, 1H), 6.68 (d, J=2.9 Hz, 1H), 4.58 (s, 2H), 3.71 (t, J=5.9 Hz, 2H), 3.01 (t, J=5.9 Hz, 2H), 2.68 (s, 3H)

Workup

filtrationThe solids were filtered off
washrinsed with EtOAc
washThe EtOAc portion was washed with a H2O/brine mixture, H2O, brine
dry with materialdried with anhydrous Na2SO4
customevaporated to an oil
customThe oil was chromatographed
washeluting with CHCl3/EtOAc
customthe resulting solid triturated with EtOAc/hexane

Sources & evidence

ORD record: ord-97bdcb257bec45c0b9018131571a23a7
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889870B2

Reaction notes

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