Hydrochloric Acid → 3-methyl-5-(2-morpholin-4-yl-ethyl)-1,5,6,7-tetrahydro-Pyrrolo[3,2-c]pyridin-4-one

HRID 2365005Notes

Reaction equation

HRID 2365005 reaction equation
C([O:3][C:4]([C:6]1[C:10]([CH3:11])=[CH:9][NH:8][C:7]=1[CH2:12][CH2:13][NH:14][CH2:15][CH2:16][N:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1)=O)C.C[Al](C)C.Cl.[OH-].[Na+]>C1(C)C=CC=CC=1.O>[CH3:11][C:10]1[C:6]2[C:4](=[O:3])[N:14]([CH2:15][CH2:16][N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[CH2:13][CH2:12][C:7]=2[NH:8][CH:9]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 16682925TrimethylaluminumHCID 666083244-methyl-2-[2-(2-morpholin-4-yl-ethylamino)-ethyl]-1H-pyrrole-3-carboxylic acid ethyl ester

Product 1

HCID 666073783-methyl-5-(2-morpholin-4-yl-ethyl)-1,5,6,7-tetrahydro-Pyrrolo[3,2-c]pyridin-4-oneYield 87.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Procedure

A stirred solution of 4-methyl-2-[2-(2-morpholin-4-yl-ethylamino)-ethyl]-1H-pyrrole-3-carboxylic acid ethyl ester (3.08 g, 10 mmol) in 50 ml of toluene was added dropwise slowly with 2M trimethyl aluminum in toluene (10 ml, 20 mmol) under an argon atmosphere. The mixture was stirred for 1 hour at room temperature and heated to reflux for another 4 hours. The reaction mixture was cooled down to, 0° C. in ice/water bath, added with 1N hydrochloric acid (30 ml) and cold water (50 ml), and stirred for 5 minutes. The mixture was adjusted to pH12 with 10% aqueous sodium hydroxide solution and extracted with dichloromethane (40 ml×3). The combined organic extracts were washed with brine (15 ml), filtered through a pad of Celite. The filtrate was dried with anhydrous sodium sulfate, filtered and concentrated, under reduced pressure to give 3-methyl-5-(2-morpholin-4-yl-ethyl)-1,5,6,7-tetrahydro-Pyrrolo[3,2-c]pyridin-4-one (2.31 g) as a red oil which was used as such.

Workup

  1. temperatureheated
  2. temperatureto reflux for another 4 hours
  3. stirringstirred for 5 minutes
  4. extractionextracted with dichloromethane (40 ml×3)
  5. washThe combined organic extracts were washed with brine (15 ml)
  6. filtrationfiltered through a pad of Celite
  7. dry with materialThe filtrate was dried with anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated, under reduced pressure

Sources & evidence

ORD record
ord-dc3a2e02643844c3a5092362a5282267
Source dataset
uspto-grants-2014_04
Patent number
US08697692B2

Reaction notes

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