Ammonium Hydroxide → HCID 21254073, compound

HRID 1531565Notes

Reaction equation

HRID 1531565 reaction equation
[NH2:1][CH2:2][CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]3([CH3:21])[CH2:17][CH2:16][N:15]([CH2:18][CH3:19])[C:14]3=[O:20])[CH:11]=2)[NH:6][C:5]=1[C:22]1[CH:27]=[C:26]([CH3:28])[CH:25]=[C:24]([CH3:29])[CH:23]=1.CC1C=C(C2NC3C(C=2CCN[CH2:50][CH2:51][CH2:52][CH2:53][C:54]2[CH:59]=[CH:58][C:57]([NH:60][S:61]([CH3:64])(=[O:63])=[O:62])=[CH:56][CH:55]=2)=CC(C(N2CCOCC2)=O)=CC=3)C=C(C)C=1.S([O-])([O-])(=O)=O.[Mg+2].[BH4-].[Na+].[NH4+].[OH-]>CO>[CH3:28][C:26]1[CH:27]=[C:22]([C:5]2[NH:6][C:7]3[C:12]([C:4]=2[CH2:3][CH2:2][NH:1][CH2:50][CH2:51][CH2:52][CH2:53][C:54]2[CH:59]=[CH:58][C:57]([NH:60][S:61]([CH3:64])(=[O:63])=[O:62])=[CH:56][CH:55]=2)=[CH:11][C:10]([C:13]2([CH3:21])[CH2:17][CH2:16][N:15]([CH2:18][CH3:19])[C:14]2=[O:20])=[CH:9][CH:8]=3)[CH:23]=[C:24]([CH3:29])[CH:25]=1

Participants

7

Reactant 5

HCID 14923Ammonium HydroxideHCID 24083Sulfuric acid magnesium salt (1:1)HCID 4311764Sodium borohydrideHCID 21254068HCID 21254068, compoundHCID 21254082HCID 21254082, compound

Product 1

HCID 21254073HCID 21254073, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 37.0 mg (0.095 mmol) of (±)-3-[3-(2-aminoethyl)-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-1-ethyl-3-methylpyrrolidin-2-one (from Step 5), 25.3 mg (0.105 mmol) of 4-[4-(methanesulfonamido)phenyl]butyraldehyde (EXAMPLE 4), and 57.0 mg (0.475 mmol) of anhydrous magnesium sulfate was purged with nitrogen and cooled in an ice-methanol bath at about −10° to −5° C. as 0.300 mL of dry CDCl3 was added gradually by syringe. The mixture was stirred under nitrogen at this temperature for 15-20 minutes. The septum was removed just long enough to add 4.5 mg (0.12 mmol) of sodium borohydride, and the solution was repurged with nitrogen. The mixture was stirred at −10° to −5° C. as 0.200 mL of dry methanol was added gradually, and stirring was continued at this temperature. After 25 minutes, the mixture was partitioned between 5 mL of ethyl acetate and 5 mL of water. The ethyl acetate layer was washed with brine, then dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by preparative TLC on Analtech tapered silica gel GF plates (developed in 92.5:7.5:0.75 CH2Cl2-MeOH-concd. NH4OH). Isolation of the product band (by extraction with the same solvent) gave 32.3 mg (55%) of a pale yellow, stiff foam; homogeneous by TLC in 92.5:7.5:0.75 CH2Cl2-MeOH-concd. NH4OH. 500 MHz 1H NMR (CDCl3) was consistent with the assigned structure. Mass spectrum (ESI): m/e=615.4 (M+H).

Workup

  1. customwas purged with nitrogen
  2. temperaturecooled in an ice-methanol bath at about −10° to −5° C. as 0.300 mL of dry CDCl3
  3. additionwas added gradually by syringe
  4. customThe septum was removed just long enough
  5. additionwas added gradually
  6. stirringstirring
  7. waitAfter 25 minutes
  8. customthe mixture was partitioned between 5 mL of ethyl acetate and 5 mL of water
  9. washThe ethyl acetate layer was washed with brine
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by preparative TLC on Analtech
  14. extractionIsolation of the product band (by extraction with the same solvent)
  15. customgave 32.3 mg (55%) of a pale yellow, stiff foam

Sources & evidence

ORD record
ord-3b513564283b412da94196887a670220
Source dataset
uspto-grants-2001_03
Patent number
US06197975B1

Reaction notes

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