Methanol → (R)-3-(2-aminopropyl)-1H-indole-7-carboxylic acid diethylamide

HRID 1351935Notes

Reaction equation

HRID 1351935 reaction equation
C1C2C(COC(=O)[NH:17][C@H:18]([CH3:37])[C:19]([C:21]3[C:29]4[C:24](=[C:25]([C:30](=[O:36])[N:31]([CH2:34][CH3:35])[CH2:32][CH3:33])[CH:26]=[CH:27][CH:28]=4)[NH:23][CH:22]=3)=O)C3C(=CC=CC=3)C=2C=CC=1.[BH4-].[Na+].CO>C(#N)C.CC(O)C>[CH2:34]([N:31]([CH2:32][CH3:33])[C:30]([C:25]1[CH:26]=[CH:27][CH:28]=[C:29]2[C:24]=1[NH:23][CH:22]=[C:21]2[CH2:19][C@H:18]([NH2:17])[CH3:37])=[O:36])[CH3:35]

Participants

6

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 69458837(R)-[2-(7-diethylcarbamoyl-1H-indol-3-yl)-1-methyl-2-oxoethyl]carbamic acid 9H-fluoren-9-ylmethyl ester

Product 1

HCID 69457261(R)-3-(2-aminopropyl)-1H-indole-7-carboxylic acid diethylamideYield 66%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of (R)-[2-(7-diethylcarbamoyl-1H-indol-3-yl)-1-methyl-2-oxoethyl]carbamic acid 9H-fluoren-9-ylmethyl ester (10.24 g, 20.1 mmol) in a mixture of acetonitrile (134 mL) and 2-propanol (7.7 ml) is added sodium borohydride (3.80 g, 100 mmol) in portions at room temperature with stirring, and the mixture is refluxed for 4 hours. The reaction solution is cooled to room temperature, and thereto is added dropwise methanol (200 ml). The reaction mixture is concentrated to dryness under reduced pressure. To the residue are added ethyl acetate and water, and the mixture is stirred. The organic layer is separated, washed with a saturated brine, and dried over anhydrous sodium sulfate. The solvent is evaporated under reduced pressure, and the residue is purified by silica gel column chromatography (methanol/(a saturated ammonia solution in chloroform)=1/100) to give the desired (R)-3-(2-aminopropyl)-1H-indole-7-carboxylic acid diethylamide (3.60 g, yield: 66%).

Workup

  1. temperaturethe mixture is refluxed for 4 hours
  2. concentrationThe reaction mixture is concentrated to dryness under reduced pressure
  3. additionTo the residue are added ethyl acetate and water
  4. stirringthe mixture is stirred
  5. customThe organic layer is separated
  6. washwashed with a saturated brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe solvent is evaporated under reduced pressure
  9. customthe residue is purified by silica gel column chromatography (methanol/(a saturated ammonia solution in chloroform)=1/100)

Sources & evidence

ORD record
ord-156e996847124439a0efd29a1fa155b3
Source dataset
uspto-grants-2007_05
Patent number
US07217724B2

Reaction notes

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