N-bromobutanimide → 6-Bromo-4-(2,5-difluorobenzyl)-1,2,3,4-tetrahydro-[1,8]naphthyridine

HRID 659468Notes

Reaction equation

HRID 659468 reaction equation
[F:1][C:2]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:3]=1[CH2:4][CH:5]1[C:14]2[C:9](=[N:10][CH:11]=[CH:12][CH:13]=2)[NH:8][CH2:7][CH2:6]1.[Br:20]N1C(=O)CCC1=O>C(Cl)Cl.C(O)(=O)C>[Br:20][C:12]1[CH:13]=[C:14]2[C:9](=[N:10][CH:11]=1)[NH:8][CH2:7][CH2:6][CH:5]2[CH2:4][C:3]1[CH:15]=[C:16]([F:19])[CH:17]=[CH:18][C:2]=1[F:1]

Participants

4

Reactant 2

HCID 67184N-bromobutanimideHCID 578858894-(2,5-Difluorobenzyl)-1,2,3,4-tetrahydro-[1,8]naphthyridine

Product 1

HCID 578858006-Bromo-4-(2,5-difluorobenzyl)-1,2,3,4-tetrahydro-[1,8]naphthyridine

Reagents, catalysts & solvents 1

HCID 21922555Acetic acid methylene chlorideSolvent

Procedure

To a solution of 4-(2,5-difluorobenzyl)-1,2,3,4-tetrahydro-[1,8]naphthyridine (23 mg) in CH2Cl2/acetic acid (5.5 mL, 10:1, v/v) was added N-bromosuccinimide (18.8 mg, 1.2 eq). The reaction was stirred at room temperature for one (1) hour, concentrated under reduced pressure, and purified by silica gel chromatography using a gradient of 0-60% ethyl acetate/hexane as the eluting solvent to give the title compound as a clear, colorless oil (30% yield). LCMS: m/z=339 (M+H+), 1H-NMR (CDCl3, 400 MHz) δ 1.66-1.75 (m, 1H), 1.75-1.86 (m, 1H), 2.73 (dd, J=9.6 and 13.4 Hz, 1H), 2.95 (dd, J=6.0 and 13.4 Hz, 1H), 2.99-3.08 (m, 1H), 3.34-3.43 (m, 1H), 3.45-3.55 (m, 1H), 5.22 (bs, 1H), 6.80-6.86 (m, 1H), 6.88-6.96 (m, 1H), 6.98-7.05 (m, 1H), 7.16 (d, J=1.9 Hz, 1H), 7.91 (d, J=1.9 Hz, 1H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-1dcfa89e6436498aa90a5d9aecef4f45
Source dataset
uspto-grants-2011_12
Patent number
US08080561B2

Reaction notes

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