4-Quinolinecarboxaldehyde → N-[3-(2-fluoro-4'-{[(quinolin-4-ylmethyl)-amino]-methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide

HRID 1064436Notes

Reaction equation

HRID 1064436 reaction equation
[NH2:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([N:15]3[CH2:19][CH:18]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:17][C:16]3=[O:25])=[CH:11][C:10]=2[F:26])=[CH:5][CH:4]=1.[N:27]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:30]([CH:37]=O)=[CH:29][CH:28]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.CN(C=O)C>[F:26][C:10]1[CH:11]=[C:12]([N:15]2[CH2:19][CH:18]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:17][C:16]2=[O:25])[CH:13]=[CH:14][C:9]=1[C:6]1[CH:7]=[CH:8][C:3]([CH2:2][NH:1][CH2:37][C:30]2[C:31]3[C:36](=[CH:35][CH:34]=[CH:33][CH:32]=3)[N:27]=[CH:28][CH:29]=2)=[CH:4][CH:5]=1

Participants

6

Reactant 3

HCID 780724-QuinolinecarboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 22274193N-[3-(4'-Aminomethyl-2-fluoro-biphenyl-4-yl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide

Product 1

HCID 22274145N-[3-(2-fluoro-4'-{[(quinolin-4-ylmethyl)-amino]-methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-ylmethyl]-acetamideYield 66%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution of amine 54 (36 mg, 0.1 mmol) in a mixture of THF and DMF (3:1, v/v) was treated with quinoline-4-carboxaldehyde (16 mg, 0.1 mmol, 1.0 equiv) at 25° C. under argon, and the resulting reaction mixture was stirred at 25° C. for 30 min before being treated with sodium triacetoxyborohydride (NaB(OAc)3H, 33 mg, 0.15 mmol, 1.5 equiv) at 25° C. The reaction mixture was subsequently stirred at 25° C. for 6 h. When TLC and HPLC showed the reductive amination reaction was complete, the reaction mixture was concentrated in vacuo. The residue was then directly purified by flash column chromatography (0-7% MeOH—CH2Cl2 gradient elution) to produce the desired N-[3-(2-fluoro-4′-{[(quinolin-4-ylmethyl)-amino]-methyl}-biphenyl-4-yl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide 4016 (32.9 mg, 66% yield) as pale-yellow oil, which solidified upon standing at room temperature in vacuo. 1H NMR (300 MHz, DMSO-d6) δ 1.85 (s, 3H, COCH3), 3.44 (t, 2H, J=5.4 Hz), 3.79 (dd, 1H, J=6.4, 9.2 Hz), 3.88 (s, 2H), 4.17 (t, 1H, J=9.1 Hz), 4.30 (s, 2H), 4.77 (m, 1H), 7.41 (dd, 1H, J=2.0, 8.0 Hz), 7.51-7.63 (m, 8H, aromatic-H), 7.74 (t, 1H, J=8.0 Hz), 8.04 (d, 1H, J=8.0 Hz), 8.18 (d, 1H, J=8.0 Hz), 8.27 (t, 1H, J=5.8 Hz, NHCOCH3), 8.87 (d, 1H, J=8.0 Hz). LCMS (ESI) m/e 499 (M+H)+.

Workup

  1. customthe resulting reaction mixture
  2. stirringThe reaction mixture was subsequently stirred at 25° C. for 6 h
  3. customamination reaction
  4. concentrationthe reaction mixture was concentrated in vacuo
  5. customThe residue was then directly purified by flash column chromatography (0-7% MeOH—CH2Cl2 gradient elution)

Sources & evidence

ORD record
ord-34cfaa792cd046c2b7aeb46c8dd93e2d
Source dataset
uspto-grants-2005_11
Patent number
US06969726B2

Reaction notes

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