Water → 2-((3-fluorophenoxy)methyl)-7,8-dihydro-1,6-naphthyridin-5(6H)-one

HRID 533153Notes

Reaction equation

HRID 533153 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:27]=[CH:28][CH:29]=1)[O:5][CH2:6][C:7]1[CH:16]=[CH:15][C:14]2[C:13](=[O:17])[N:12](CC3C=CC(OC)=CC=3)[CH2:11][CH2:10][C:9]=2[N:8]=1.O.[N+]([O-])([O-])=O.[NH4+].[Ce].S(NN)(C1C=CC(C)=CC=1)(=O)=O>CC#N>[F:1][C:2]1[CH:3]=[C:4]([CH:27]=[CH:28][CH:29]=1)[O:5][CH2:6][C:7]1[CH:16]=[CH:15][C:14]2[C:13](=[O:17])[NH:12][CH2:11][CH2:10][C:9]=2[N:8]=1

Participants

6

Reactant 4

HCID 962WaterHCID 15303P-ToluenesulfonylhydrazideHCID 57418452Ammonium cerium-nitrateHCID 680083842-((3-fluorophenoxy)methyl)-6-(4-methoxybenzyl)-7,8-dihydro-1,6-naphthyridin-5(6H)-one

Product 1

HCID 680079902-((3-fluorophenoxy)methyl)-7,8-dihydro-1,6-naphthyridin-5(6H)-oneYield 76%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

2-((3-Fluorophenoxy)methyl)-6-(4-methoxybenzyl)-7,8-dihydro-1,6-naphthyridin-5(6H)-one (300 mg, 0.77 mmol) from above was dissolved in CH3CN (5 mL) and water (2 mL) added. Cerium ammonium nitrate (419 mg, 0.77 mmol) was added and after 15 min, the reaction was partitioned between EtOAc (10 mL) and brine (10 mL). The organic layers were concentrated and purified by RP-HPLC (0 to 90% CH3CN). Product containing fractions were treated with PS-TsNHNH2 (2 equiv) to give the compound as a solid (74 mg, 76%). 1H NMR (400 MHz, CDCl3) δ 8.38 (1H, d, J=8), 7.56 (1H, d, J=8), 7.27 (1H, dd, J=16, 7.6), 6.77 (1H, dd, J=13.2, 2.0), 6.71 (2H, m), 5.96 (1H, br s), 5.20 (2H, s), 3.67 (2H, t, J=6.2H), 5.96 (1H, br s), 5.20 (2H, s), 3.67 (2H, t, J=6.8 Hz), 3.24 (2H, t, J=6.8 Hz); LC-MS (M+H)=273.2.

Workup

  1. customthe reaction was partitioned between EtOAc (10 mL) and brine (10 mL)
  2. concentrationThe organic layers were concentrated
  3. custompurified by RP-HPLC (0 to 90% CH3CN)
  4. additionProduct containing fractions

Sources & evidence

ORD record
ord-1e856fa8eba34e7898f4f85ab6f4d60c
Source dataset
uspto-grants-2014_10
Patent number
US08853237B2

Reaction notes

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