Acetic Acid → HCID 22638732, compound

HRID 1836619Notes

Reaction equation

HRID 1836619 reaction equation
C([BH3-])#N.[Na+].[C:5]([C@@H:8]1[CH2:10][C@H:9]1[C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:20]#[N:21])[CH:18]=2)[N:13](S(C2C=CC(C)=CC=2)(=O)=O)[CH:12]=1)(=O)[CH3:6].[CH3:32][NH:33][CH3:34].C(O)(=O)C.[OH-].[Na+]>CC(O)C.[Cl-].[Na+].O.O.C(O)C>[CH3:32][N:33]([CH3:34])[CH:5]([CH:8]1[CH2:10][CH:9]1[C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:20]#[N:21])[CH:18]=2)[NH:13][CH:12]=1)[CH3:6]

Participants

10

Reactant 5

HCID 176Acetic AcidHCID 674DimethylamineHCID 14798Sodium Hydroxide2×HCID 5003444Sodium cyanoborohydrideHCID 69846031HCID 69846031, compound

Product 1

HCID 22638732HCID 22638732, compoundYield 100.2%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 3776IsopropanolSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
50 °C

Procedure

Sodium cyanoborohydride (51 mg, 0.792 mmol, 3 equiv) was added to a stirred mixture of trans-3-(2-acetyl-cyclopropyl)-1-(toluene-4-sulfonyl)-1H-indole-5-carbonitrile (100 mg, 0.264 mmol), dimethylamine (2.0 M in THF, 2.64 ml, 5.28 mmol, 20 equiv), acetic acid (302 uL, 5.28 mmol, 20 equiv) and powdered 4 A molecular sieves (150 mg, actived) in 2-propanol (2.0 ml). The resulting mixture was stirred at 50° C. for 20 h. Ethanol (5 ml), water (0.5 ml), and a solution of sodium hydroxide (10 M in water, 0.6 ml) were added to the reaction. The mixture was heated with stirring at 50° C. for 1 h. The reaction contents were poured into an aqueous solution of sodium hydroxide (1 M, 25 ml) and brine (25 ml). The aqueous layer was extracted with ethyl acetate (3×100 ml). The combined organic extracts were washed with brine (20 ml), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The crude product was purified using silica gel column chromatography (90:10:1, CHCl3/MeOH/Et3N) to provide 67 mg (100% yield) of 3-[2-(1-dimethylamino-ethyl)-cyclopropyl]-1H-indole-5-carbonitrile as a 1:1 mixture of diastereomers. viscous oil: LC-MS (column=Phenomenex Luna C18 S10, 3×50 mm, start %B=0, final %B=100, gradient time=3 min, flow rate=4 ml/min) m/e 254 (M+H)+, tR 1.19 min.

Workup

  1. temperatureThe mixture was heated
  2. stirringwith stirring at 50° C. for 1 h
  3. customThe reaction contents
  4. extractionThe aqueous layer was extracted with ethyl acetate (3×100 ml)
  5. washThe combined organic extracts were washed with brine (20 ml)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified

Sources & evidence

ORD record
ord-9d760a927be0426ebb53d56329ef6b7e
Source dataset
uspto-grants-2004_08
Patent number
US06777437B2

Reaction notes

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