Acetic Acid → HCID 178484130, compound

HRID 865705Notes

Reaction equation

HRID 865705 reaction equation
N[C@H:2]1[CH2:5][C@H:4]([C:6]2[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([CH2:15][N:16]4[CH:20]=[N:19][CH:18]=[N:17]4)[CH:13]=3)[NH:8][CH:7]=2)[CH2:3]1.[C:21]([BH3-])#[N:22].[Na+].[C:25](O)(=O)C.C=O.[C:31](=O)([O-])[O-].[K+].[K+]>CO>[CH3:25][N:22]([CH3:21])[C@H:2]1[CH2:5][C@@H:4]([C:6]2[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([CH2:15][N:16]4[CH:20]=[N:19][CH:18]=[N:17]4)[CH:13]=3)[NH:8][CH:7]=2)[CH2:3]1.[CH3:31][N:22]([CH3:21])[C@H:2]1[CH2:5][C@H:4]([C:6]2[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([CH2:15][N:16]4[CH:20]=[N:19][CH:18]=[N:17]4)[CH:13]=3)[NH:8][CH:7]=2)[CH2:3]1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 11430Potassium CarbonateHCID 5003444Sodium cyanoborohydrideHCID 178511728HCID 178511728, compound

Product 2

HCID 178484129HCID 178484129, compoundYield 34%HCID 178484130HCID 178484130, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C.) and stirred solution of cis/trans-3-(1-aminocyclobutan-3-yl)-5-[(1,2,4-triazol-1-yl)methyl]- 1H-indole (270 mg, 1.0 mmol) in anhydrous methanol (20 ml) were added sodium cyanoborohydride (127 mg, 2.0 mmol), glacial acetic acid (289 μl, 5.0 mmol) and a solution of formaldehyde (38% w/v aqueous solution; 200 μl) in absolute methanol (3 ml). The reaction mixture was then allowed to warm to room temperature and it was stirred for 1.5 hours before saturated aqueous potassium carbonate (10 ml) was added and the methanol was removed under vacuum. The aqueous residue was extracted with ethyl acetate (3×50 ml) and the combined organic solutions were washed with brine (2×15 ml), dried (Na2SO4) and concentrated. The remaining residue was purified by preparative TLC (silica gel, dichloromethane-methanol-ammonia, 90:10:1) to give 102 mg (34%) of 3-[cis-1-(dimethylamino)cyclobutan-3-yl]-5-[(1,2,4-triazol-1-yl)methyl]-1H-indole (less polar isomer) and 132 mg (44%) of 3-[trans-1-(dimethyl amino)cyclobutan-3-yl]-5-[(1,2,4-triazol-1-yl) methyl]-1H-indole (more polar isomer). The hydrogen oxalate salts were prepared and showed:

Workup

  1. temperatureto warm to room temperature
  2. additionwas added
  3. customthe methanol was removed under vacuum
  4. extractionThe aqueous residue was extracted with ethyl acetate (3×50 ml)
  5. washthe combined organic solutions were washed with brine (2×15 ml)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe remaining residue was purified by preparative TLC (silica gel, dichloromethane-methanol-ammonia, 90:10:1)

Sources & evidence

ORD record
ord-90a910ed8120430f8733e30c4af43d64
Source dataset
uspto-grants-1996_10
Patent number
US05567726

Reaction notes

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