Acetic Acid → 3-(2-Thienyl)-1,6-naphthyridine

HRID 732871Notes

Reaction equation

HRID 732871 reaction equation
CO[C:3]1[N:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]=[C:6]([C:21]1[S:22][CH:23]=[CH:24][CH:25]=1)[C:7](C1C=CC(C=O)=CC=1)=[N:8]2.Cl.Cl.N1CCC(C2N=C(C3C=CC=CN=3)NN=2)CC1.C(N(CC)CC)C.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>[Cl-].[NH4+].CN(C=O)C>[S:22]1[CH:23]=[CH:24][CH:25]=[C:21]1[C:6]1[CH:7]=[N:8][C:9]2[C:4]([CH:5]=1)=[CH:3][N:12]=[CH:11][CH:10]=2

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 578388384-[5-Methoxy-3-(2-thienyl)-1,6-naphthyridin-2-yl]benzaldehydeHCID 1784785342-(5-Piperidin-4-yl-4h-1,2,4-triazol-3-yl)-pyridine dihydrochloride

Product 1

HCID 700068873-(2-Thienyl)-1,6-naphthyridine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
23 °C

Procedure

A 25 ml RB flask with a stirring bar was charged with 4-[5-methoxy-3-(2-thienyl)-1,6-naphthyridin-2-yl]benzaldehyde (1-5) (62 mg, 0.18 mmol), followed by 2-(3-piperidin-4-yl-1H-1,2,4-triazol-5-yl)pyridine dihydrochloride (1-6) (82 mg, 0.36 mmol), anhydrous DMF (1.0 mL), triethylamine (72 mg, 0.716 mmol), and acetic acid (107 mg, 1.79 mmol). Then sodium triacetoxyborohydride (76 mg, 0.36 mmol) was added in one portion, and the resulting pale yellow solution was stirred at 23° C. overnight. The mixture was diluted with sat. ammonium chloride solution (10 mL), extracted twice with ethyl acetate (10 mL). The crude mixture was purified by column chromatography on silica gel (0-30% methanol/dichloromethane) to give 5-methoxy-2(4-{[4-5-pyridin-2-yl-4H-1,2,4-triazol)piperidin-1-yl]methyl}phenyl)-3-(2-thienyl)-1,6-naphthyridine (1-7). 1H NMR (CDCl3, ppm) δ: 8.54 (bs, 1H), 8.51 (s,1H), 8.10 (d, J=6.0 Hz, 1H), 8.01 (d, J=7.8 Hz, 1H), 7.68 (t, J=7.7 Hz, 1H), 7.42 (d, J=8.0 Hz, 2H), 7.37 (d, J=6.9 Hz, 1H), 7.29 (d, J=8.0 Hz, 2H), 7.25 (t, J=3.4 Hz, 1H), 7.19 (d, J=5.1 Hz, 1H), 7.15 (s, 1H), 6.81 (t, J=3.6 Hz, 1H), 6.68 (d, J=3.1 Hz, 1H), 4.05 (s, 3H), 3.98 (s, 2H), 3.35 (s, 1H), 3.25 (bs, 2H), 3.02 (bs, 2H), 2.75 (bs, 2H), 2.19 (bs, 2H).

Workup

  1. extractionextracted twice with ethyl acetate (10 mL)
  2. customThe crude mixture was purified by column chromatography on silica gel (0-30% methanol/dichloromethane)

Sources & evidence

ORD record
ord-ed12f82f6d4d4a6881779a39225a7cba
Source dataset
uspto-grants-2009_09
Patent number
US07589068B2

Reaction notes

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