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

HRID 1007648Notes

Reaction equation

HRID 1007648 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].C(O)(=O)C.[CH3:34][S:35]([N:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1)(=[O:37])=[O:36].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:41]3[CH2:42][CH2:43][N:38]([S:35]([CH3:34])(=[O:37])=[O:36])[CH2:39][CH2:40]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])([CH3:3])([CH3:4])[CH3:2]

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 22285142N-methanesulfonylpiperazine acetic acid salt

Product 1

HCID 121116905-(4-Methanesulfonyl-piperazin-1-ylmethyl)-2-(2-oxo-1,2-dihydro-quinolin-3-yl)-indole-1-carboxylic acid tert-butyl ester

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-methanesulfonylpiperazine acetic acid salt (4.62 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 3h. The reaction stopped at 76% of conversion and treated with MgSO4 and additional 1 g of the hydride. After further stirring for 1h 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 dimethylformamide and treated with the activated carbon. The filtrate solution (celite) was concentrated to syrup which was quickly trituated with methanol (100 mL). The resulting solid was collected by filtration, redissolved in dimethylformamide, concentrated to syrup, trituated with methanol (100 mL), collected by filtration and vacuum-dried to give 5-(4-Methanesulfonyl-piperazin-1-ylmethyl)-2-(2-oxo-1,2-dihydro-quinolin-3-yl)-indole-1-carboxylic acid tert-butyl ester (5-9) as a white powder, 1H NMR (500 MHz, DMSO-d6) δ 12.06 (s, 1H), 8.06 (s, 1H), 8.04 (d, 1H, J=8.5 Hz), 7.74 (d, 1H, J=8.0 Hz), 7.55 (s, 1H), 7.53 (dt, 1H, J=8.0, 1.5 Hz), 7.35 (d, 1H, J=8.5 Hz), 7.30 (dd, 1H, J=8.5, 1.5 Hz), 7.22 (t, 1H, J=7.5 Hz), 6.76 (s, 1H), 3.62 (s, 2H), 3.16 (m, 4H), 2.87 (s, 3H), 2.48 (m, 4H), 1.35 (s, 9H).

Workup

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

Sources & evidence

ORD record
ord-0f64dc75e1bc44b6a23ff97bdf796189
Source dataset
uspto-grants-2004_09
Patent number
US06794393B1

Reaction notes

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