Sulfuric acid magnesium salt (1:1) → 5-[4-(2-Hydroxy-ethanoyl)-piperazin-1-ylmethyl]-2-(2-oxo-1,2-dihydro-quinolin-3-yl)-indole-1-carboxylic acid tert-butyl ester

HRID 431171Notes

Reaction equation

HRID 431171 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH:17]=O)=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:19]1[C:20](=[O:29])[NH:21][C:22]2[C:27]([CH:28]=1)=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH:30][CH2:31][C:32]([N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1)=[O:33].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[O-]S([O-])(=O)=O.[Mg+2].[H-]>ClC(Cl)C.C(O)(=O)C>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH2:17][N:37]3[CH2:38][CH2:39][N:34]([C:32](=[O:33])[CH2:31][OH:30])[CH2:35][CH2:36]3)=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:19]1[C:20](=[O:29])[NH:21][C:22]2[C:27]([CH:28]=1)=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 166653HydrideHCID 5049666Sodium triacetoxyborohydrideHCID 121116895-Formyl-2-(2-oxo-1,2-dihydro-quinolin-3-yl)-indole-1-carboxylic acid tert-butyl esterHCID 185068842-Hydroxy-1-(piperazin-1-yl)ethan-1-one

Product 1

HCID 206073155-[4-(2-Hydroxy-ethanoyl)-piperazin-1-ylmethyl]-2-(2-oxo-1,2-dihydro-quinolin-3-yl)-indole-1-carboxylic acid tert-butyl esterYield 57%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 63651,1-DichloroethaneSolvent

Procedure

To a stirred solution of the aldehyde (5-8, 2.01 g, 5.15 mmol, 1 equiv) and N-(2-hydroxyacetyl)piperazine (2.97 g, 20.60 mmol, 4 equiv) in dichloroethane (400 mL) was added at ambient temperature acetic acid (1.2 mL). The reaction mixture was treated with sodium triacetoxyborohydride and stirred for 3 h. The reaction stopped at 76% of conversion and treated with MgSO4 and additional 1 g of the hydride. After further stirring for 1 h the reaction was complete. The reaction mixture was partitioned between ethyl acetate and saturated aqueous NaHCO3. The organic layer was once again washed with saturated aqueous NaHCO3, and then with brine, separated, dried with (Na2SO4) and concentrated in vacuo. The crude solid was dissolved in N,N-dimethylformamide and treated with the activated carbon. The filtrate solution (celite) was concentrated to syrup which was quickly triturated with methanol (100 mL). The resulting solid was collected by filtration, redissolved in N,N-dimethylformamide, concentrated to syrup, triturated with methanol (100 mL), collected by filtration and vacuum-dried to give 5-[4-(2-hydroxy-ethanoyl)-piperazin-1-ylmethyl]-2-(2-oxo-1,2-dihydro-quinolin-3-yl)-indole-1-carboxylic acid tert-butyl ester (5-9, 1.51 g, 57%) as a white powder; 1H NMR (500 MHz, DMSO-d6) δ 12.24 (br s, 1H), 8.21 (d, 1H, J=8.7 Hz), 7.91 (s, 1H), 7.61 (d, 1H, J=6.9 Hz), 7.52 (s, 1H), 7.49 (m, 1H), 7.36 (d, 1H, J=8.1 Hz), 7.33 (dd, 1H, J=8.4, 1.5 Hz), 7.24 (m, 1H), 6.67 (s, 1H), 4.15 (s, 2H), 3.69 (m, 2H), 3.65 (s, 2H), 3.28 (m, 2H), 2.49 (m, 4H), 1.40 (s, 9H).

Workup

  1. stirringAfter further stirring for 1 h the reaction
  2. customThe reaction mixture was partitioned between ethyl acetate and saturated aqueous NaHCO3
  3. washThe organic layer was once again washed with saturated aqueous NaHCO3
  4. customwith brine, separated
  5. dry with materialdried with (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. dissolutionThe crude solid was dissolved in N,N-dimethylformamide
  8. additiontreated with the activated carbon
  9. concentrationThe filtrate solution (celite) was concentrated to syrup which
  10. customwas quickly triturated with methanol (100 mL)
  11. filtrationThe resulting solid was collected by filtration
  12. dissolutionredissolved in N,N-dimethylformamide
  13. concentrationconcentrated to syrup
  14. customtriturated with methanol (100 mL)
  15. filtrationcollected by filtration
  16. customvacuum-dried

Sources & evidence

ORD record
ord-01e8087afcc34162b7fae5f1c552e67a
Source dataset
uspto-grants-2003_12
Patent number
US06656942B2

Reaction notes

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