Diisopropylethylamine → (S)-6-Chloro-4-[1-(1-naphthalen-2-yl-ethyl)-piperdin-4-ylamino]-chromen-2-one

HRID 897226Notes

Reaction equation

HRID 897226 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C@@H:11]([N:13]1[CH2:18][CH2:17][CH:16]([NH2:19])[CH2:15][CH2:14]1)[CH3:12].C(N(C(C)C)CC)(C)C.[Cl:29][C:30]1[CH:31]=[C:32]2[C:37](=[CH:38][CH:39]=1)[O:36][C:35](=[O:40])[CH:34]=[C:33]2OS(C(F)(F)F)(=O)=O>C1COCC1>[Cl:29][C:30]1[CH:31]=[C:32]2[C:37](=[CH:38][CH:39]=1)[O:36][C:35](=[O:40])[CH:34]=[C:33]2[NH:19][CH:16]1[CH2:17][CH2:18][N:13]([C@H:11]([C:2]2[CH:3]=[CH:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:1]=2)[CH3:12])[CH2:14][CH2:15]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 20817849HCID 20817849, compoundHCID 29009336(s)-1-(1-Naphthalen-2-yl-ethyl)-piperidin-4-ylamine

Product 1

HCID 60018712(S)-6-Chloro-4-[1-(1-naphthalen-2-yl-ethyl)-piperdin-4-ylamino]-chromen-2-oneYield 25%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of (S)-1-(1-naphthalen-2-yl-ethyl)-piperidin-4-ylamine (0.24 g, 0.94 mmol) and diisopropylethylamine (0.34 mL, 2 mmol) in 5 mL THF was added trifluoromethanesulfonic acid 6-chloro-2-oxo-2H-chromen-4-yl ester (0.30 g, 0.93 mmol). The reaction was stirred at room temperature for about 3 hours. The reaction mixture was then washed with water, dried with MgSO4 and evaporated. The residue was purified by chromatography on silica gel with methanol/dichloromethane (2:98) to give the title compound (0.1 g, 25%). The final product was converted to the mono-HCl salt by addition of 1.0N HCl in ether to a suspension of the compound in dichloromethane. The solvent was removed by evaporation. 1H NMR of the mono-HCl salt (300 MHz, DMSO-d6) δ 1.20-1.28 (2H, m), 1.81 (3H, d, J=6.97 Hz), 1.74-2.18 (4H, m), 2.83-3.05 (2H, m), 3.30-3.80 (2H, m), 4.65-4.78 (1H, br), 5.37 (1H, s), 7.30-7.79 (5H, m), 7.92-8.16 (4H, m), 8.32 (1H, d, J=2.64 Hz), 10.09 (1H, br, s).

Workup

  1. washThe reaction mixture was then washed with water
  2. dry with materialdried with MgSO4
  3. customevaporated
  4. customThe residue was purified by chromatography on silica gel with methanol/dichloromethane (2:98)

Sources & evidence

ORD record
ord-d1c13239487640b69bb46bfe0297c5ad
Source dataset
uspto-grants-2005_07
Patent number
US06921821B2

Reaction notes

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