Malic Acid → HCID 67532208, compound

HRID 2068749Notes

Reaction equation

HRID 2068749 reaction equation
[OH:1][CH:2]([CH2:6][C:7]([OH:9])=[O:8])[C:3]([OH:5])=[O:4].[F:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][C:15](=[O:20])/[C:14]/2=[CH:21]\[C:22]1[NH:30][C:29]2[CH2:28][CH2:27][N:26]([CH2:31][C@H:32]([OH:40])[CH2:33][N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)[C:25](=[O:41])[C:24]=2[C:23]=1[CH3:42].O>CO.C(#N)C>[C:3]([OH:5])(=[O:4])[CH:2]([CH2:6][C:7]([OH:9])=[O:8])[OH:1].[F:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][C:15](=[O:20])/[C:14]/2=[CH:21]\[C:22]1[NH:30][C:29]2[CH2:28][CH2:27][N:26]([CH2:31][C@H:32]([OH:40])[CH2:33][N:34]3[CH2:35][CH2:36][O:37][CH2:38][CH2:39]3)[C:25](=[O:41])[C:24]=2[C:23]=1[CH3:42]

Participants

6

Reactant 3

HCID 525Malic AcidHCID 962WaterHCID 25207322HCID 25207322, compound

Product 1

HCID 67532208HCID 67532208, compoundYield 99%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6342AcetonitrileSolvent

Procedure

2-Hydroxy-succinic acid (231 mg, 1.72 mmol) was dissolved in 100 mL of methanol under stirring at room temperature, and (R,Z)-2-(5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one 1 (560 mg, 1.233 mmol), 200 mL of methanol and 100 mL of water was then added to the solution in batch. Upon completion of the addition, the reaction system was heated at 50° C. in an oil bath in dark until a clear solution was obtained. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to remove the solvent to give a yellow solid. The resulting solid was dissolved in 100 mL of acetonitrile, and the mixture was heated to reflux in dark for 1.5 hours. The oil bath was removed. The reaction system was naturally cooled down to room temperature and filtered to give the title compound (R,Z)-2-(5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one malate 24 (718 mg, yield 99%) as a yellow solid.

Workup

  1. additionUpon completion of the addition
  2. temperaturethe reaction system was heated at 50° C. in an oil bath in dark until a clear solution
  3. customwas obtained
  4. filtrationThe reaction mixture was filtered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customto remove the solvent
  7. customto give a yellow solid
  8. temperaturethe mixture was heated
  9. temperatureto reflux in dark for 1.5 hours
  10. customThe oil bath was removed
  11. temperatureThe reaction system was naturally cooled down to room temperature
  12. filtrationfiltered

Sources & evidence

ORD record
ord-4500729c1c1145fca32e6b490e14229e
Source dataset
uspto-grants-2012_10
Patent number
US08299069B2

Reaction notes

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