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 456911Notes

Reaction equation

HRID 456911 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 3 hours. The reaction stopped at 76% of conversion and treated with MgSO4 and additional 1 g of the hydride. After further stirring for 1 hour 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. stirringAfter further stirring for 1 hour 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 dimethylformamide
  8. additiontreated with the activated carbon
  9. concentrationThe filtrate solution (celite) was concentrated to syrup which
  10. filtrationThe resulting solid was collected by filtration
  11. dissolutionredissolved in dimethylformamide
  12. concentrationconcentrated to syrup
  13. filtrationcollected by filtration
  14. customvacuum-dried

Sources & evidence

ORD record
ord-c1cf40ce96864a1ea43eb2e37cc8bbe7
Source dataset
uspto-grants-2007_03
Patent number
US07186723B2

Reaction notes

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