Triethylamine → Ethyl 3-(3,4-dihydro-2,7-naphthyridin-2(1H)-yl)benzoate

HRID 1052074Notes

Reaction equation

HRID 1052074 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.C(=O)([O-])[O-].[Cs+].[Cs+].C(N(CC)CC)C.Br[C:27]1[CH:28]=[C:29]([CH:35]=[CH:36][CH:37]=1)[C:30]([O:32][CH2:33][CH3:34])=[O:31].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:11]1[C:12]2[C:7](=[CH:6][CH:5]=[N:4][CH:3]=2)[CH2:8][CH2:9][N:10]1[C:27]1[CH:28]=[C:29]([CH:35]=[CH:36][CH:37]=1)[C:30]([O:32][CH2:33][CH3:34])=[O:31]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 10796Cesium carbonate2×HCID 90488Ethyl 3-bromobenzoateHCID 634876Binap, (A+-)-HCID 691916791,2,3,4-Tetrahydro-2,7-naphthyridine dihydrochloride

Product 1

HCID 86695877Ethyl 3-(3,4-dihydro-2,7-naphthyridin-2(1H)-yl)benzoateYield 6%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 1,2,3,4-tetrahydro-2,7-naphthyridine dihydrochloride (41.4 mg, 0.20 mmol), cesium carbonate (326 mg, 1.0 mmol), and triethylamine (0.056 mL, 0.40 mmol) in 2.0 mL dioxane was warmed until the amine starting material had dissolved. The reaction filtrate was transferred into another reaction vial and the following added: a spatula portion of cesium carbonate, ethyl 3-bromobenzoate (0.032 mL, 0.20 mmol), palladium acetate (2.2 mg, 0.01 mmol) plus catalytic Pd2(dba)3, and RAC-BINAP (6.2 mg, 0.01 mmol). The reaction was heated at 95° C. for 17 hours, filtered, and evaporated to an oil. The oil was chromatograph eluting with CHCl3/EtOAc to give the title compound as a light yellow oil (3.2 mg, 6%). 1H NMR (CDCl3) δ: 8.46 (s, 1H), 8.39 (d, J=5.0 Hz, 1H), 7.66 (dd, J=2.3, 1.5 Hz, 1H), 7.54 (dt, J=7.5, 1.2 Hz, 1H), 7.35 (t, J=7.9 Hz, 1H), 7.16 (dd, J=8.4, 1.9 Hz, 1H), 7.12 (d, J=5.0 Hz, 1H), 4.46 (s, 2H), 4.39 (q, J=7.1 Hz, 2H), 3.62 (t, J=5.9 Hz, 2H), 3.01 (t, J=5.7 Hz, 2H), 1.38-1.44 (m, 3H).

Workup

  1. dissolutionhad dissolved
  2. additionfollowing added
  3. filtrationfiltered
  4. customevaporated to an oil
  5. washeluting with CHCl3/EtOAc

Sources & evidence

ORD record
ord-4f0a518933ec41b49abf8c9359f1bbe6
Source dataset
uspto-grants-2016_07
Patent number
US09388176B2

Reaction notes

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