Citric Acid → HCID 58306746, compound

HRID 1909907Notes

Reaction equation

HRID 1909907 reaction equation
[Cl:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][C:14]=3[C:16](O)=[O:17])[CH:9]=[CH:8]2)=[CH:4][CH:3]=1.Cl.[NH2:22][CH2:23][C:24]1[CH:33]=[CH:32][C:27]([C:28]([O:30]C)=[O:29])=[CH:26][C:25]=1[Cl:34].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C>[Cl:34][C:25]1[CH:26]=[C:27]([CH:32]=[CH:33][C:24]=1[CH2:23][NH:22][C:16]([C:14]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:15]=1[N:7]([CH2:6][C:5]1[CH:19]=[CH:20][C:2]([Cl:1])=[CH:3][CH:4]=1)[CH:8]=[CH:9]2)=[O:17])[C:28]([OH:30])=[O:29]

Participants

7

Reactant 5

HCID 311Citric AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58307031HCID 58307031, compoundHCID 668683641370422-30-2

Product 1

HCID 58306746HCID 58306746, compoundYield 75.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 1-(4-chlorobenzyl)-1H-indole-7-carboxylic acid (0.20 g), methyl 4-(aminomethyl)-3-chlorobenzoate hydrochloride (0.18 g), and HATU (0.32 g) in DMF (4.0 mL) was added diisopropylethylamine (0.29 ml) under ice-cooling, followed by stirring at room temperature for 14 hours. After ice-cooled again, a 5% aqueous citric acid solution (8.0 mL) was added thereto, and the precipitated solid was collected by filtration, sequentially washed with water and diisopropylether, and dried at 60° C. under reduced pressure. To the obtained solid were added methanol (3.0 mL), THF (3.0 mL), and a 1 M aqueous sodium hydroxide solution (2.0 mL), followed by stirring at 60° C. for 2 hours. The reaction mixture was left to be cooled, a 10% aqueous citric acid solution (5.0 mL) was added thereto, and the precipitated solid was collected by filtration, washed with water, and dried at 60° C. under reduced pressure to obtain 3-chloro-4-[({[1-(4-chlorobenzyl)-1H-indol-7-yl]carbonyl}amino)methyl]benzoic acid (0.24 g).

Workup

  1. temperaturecooling
  2. temperatureAfter ice-cooled again
  3. filtrationthe precipitated solid was collected by filtration
  4. washsequentially washed with water and diisopropylether
  5. customdried at 60° C. under reduced pressure
  6. additionTo the obtained solid were added methanol (3.0 mL), THF (3.0 mL)
  7. stirringby stirring at 60° C. for 2 hours
  8. waitThe reaction mixture was left
  9. temperatureto be cooled
  10. additiona 10% aqueous citric acid solution (5.0 mL) was added
  11. filtrationthe precipitated solid was collected by filtration
  12. washwashed with water
  13. customdried at 60° C. under reduced pressure

Sources & evidence

ORD record
ord-b43aceca73ab408290f9e339a3b89099
Source dataset
uspto-grants-2013_12
Patent number
US08598355B2

Reaction notes

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