Trifluoroacetic acid → 4-{[4-(4-pyridin-2-yl-1H-imidazol-1-yl)piperidin-1-yl]methyl}phenyl-1,6-naphthyridin-5(6H)-one trifluoroacetic acid salt

HRID 605013Notes

Reaction equation

HRID 605013 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:8]=[CH:9][N:10]([CH:12]2[CH2:17][CH2:16][N:15]([C:18](OC(C)(C)C)=O)[CH2:14][CH2:13]2)[CH:11]=1.[F:25][C:26]([F:31])([F:30])[C:27]([OH:29])=[O:28].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[O:46]=[C:47]1[NH:56][CH:55]=[CH:54][C:53]2[N:52]=[C:51]([C:57]3[CH:64]=[CH:63][C:60](C=O)=[CH:59][CH:58]=3)[C:50](C3C=CC=CC=3)=[CH:49][C:48]1=2>C(Cl)Cl>[F:25][C:26]([F:31])([F:30])[C:27]([OH:29])=[O:28].[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:8]=[CH:9][N:10]([CH:12]2[CH2:13][CH2:14][N:15]([CH2:18][C:60]3[CH:59]=[CH:58][C:57]([C:51]4[CH:50]=[CH:49][C:48]5[C:47](=[O:46])[NH:56][CH:55]=[CH:54][C:53]=5[N:52]=4)=[CH:64][CH:63]=3)[CH2:16][CH2:17]2)[CH:11]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 5049666Sodium triacetoxyborohydrideHCID 592646194-(5-Oxo-3-phenyl-5,6-dihydro-1,6-naphthyridin-2-yl)benzaldehydeHCID 67055580tert-butyl 4-(4-pyridin-2-yl-1H-imidazol-1-yl)piperidine-1-carboxylate

Product 1

HCID 866249434-{[4-(4-pyridin-2-yl-1H-imidazol-1-yl)piperidin-1-yl]methyl}phenyl-1,6-naphthyridin-5(6H)-one trifluoroacetic acid salt

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 4-(4-pyridin-2-yl-1H-imidazol-1-yl)piperidine-1-carboxylate (300 mg, 0.9 mmol) in CH2Cl2 (4 mL) was added trifluoroacetic acid (2 mL). The resulting solution was stirred at room temperature for 1 h. The solvents were removed in vacuo and the residue was dried under vacuum for a further 2 h. The residue was dissolved in a solution of triethylamine (1 mL) in CH2Cl2 (3 mL). The reaction mixture was stirred for 1 h at room temperature and sodium triacetoxyborohydride (381 mg, 1.8 mmol), 4-(5-oxo-3-phenyl-5,6-dihydro-1,6-naphthyridin-2-yl)benzaldehyde (295 mg, 0.9 mmol) and molecular sieves were added. Stirring was continued at room temperature for 16 h and the reaction quenched by addition of methanol. The residue was purified by HPLC (phenomenex column, 35%-100% acetonitrile/water+0.1% TFA) to afford 3-phenyl-2-(4-{[4-(4-pyridin-2-yl-1H-imidazol-1-yl)piperidin-1-yl]methyl}phenyl-1,6-naphthyridin-5(6H)-one trifluoroacetic acid salt as a yellow oil. 1H NMR (500 MHz, CD3OD) δ 8.56 (m, 3H), 8.28 (s, 1H), 8.10 (m, 1H), 7.99 (m, 1H), 7.45 (m, 1H), 7.42 (m, 5H), 7.21 (m, 3H), 7.15 (m, 2H), 6.77 (m, 1H), 4.62 (m, 1H), 4.34 (s, 2H), 3.55 (m, 2H), 3.21 (m, 2H), 2.39 (m, 4H).

Workup

  1. customThe solvents were removed in vacuo
  2. customthe residue was dried under vacuum for a further 2 h
  3. dissolutionThe residue was dissolved in a solution of triethylamine (1 mL) in CH2Cl2 (3 mL)
  4. stirringThe reaction mixture was stirred for 1 h at room temperature
  5. stirringStirring
  6. waitwas continued at room temperature for 16 h
  7. customthe reaction quenched by addition of methanol
  8. customThe residue was purified by HPLC (phenomenex column, 35%-100% acetonitrile/water+0.1% TFA)

Sources & evidence

ORD record
ord-e780c7ae37d041d193c4579887bac9dd
Source dataset
uspto-grants-2011_03
Patent number
US07910561B2

Reaction notes

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