Sodium Hydroxide → HCID 58306679, compound

HRID 1909851Notes

Reaction equation

HRID 1909851 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[C:10]([O:12]C)=O)[CH:3]=[CH:2]1.CC(C)([O-:17])C.[K+].Br[CH2:21][C:22]1[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][CH:23]=1.C(C1C=CC(CN2C3C(=CC=CC=3C(OC)=O)C=C2)=CC=1)#N.[OH-].[Na+].C(C1C=CC(CN2C3C(=CC=CC=3C(O)=O)C=C2)=CC=1)(=O)N.Cl.[NH2:77][C@H:78]([C:80]1[CH:89]=[CH:88][C:83]([C:84]([O:86][CH3:87])=[O:85])=[CH:82][CH:81]=1)[CH3:79].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.O.CO.C1COCC1>[C:26]([C:25]1[CH:28]=[CH:29][C:22]([CH2:21][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][C:8]=3[C:10]([NH:77][C@H:78]([C:80]3[CH:89]=[CH:88][C:83]([C:84]([O:86][CH3:87])=[O:85])=[CH:82][CH:81]=3)[CH3:79])=[O:12])[CH:3]=[CH:2]2)=[CH:23][CH:24]=1)(=[O:17])[NH2:27]

Participants

14

Reactant 9

HCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 869964-(Bromomethyl)benzonitrileHCID 676694Methyl indole-7-carboxylateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 23665647Potassium tert-butoxideHCID 57462942(S)-Methyl 4-(1-aminoethyl)benzoate hydrochlorideHCID 66868448HCID 66868448, compoundHCID 66868462HCID 66868462, compound

Product 1

HCID 58306679HCID 58306679, compoundYield 54.7%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of methyl 1H-indole-7-carboxylate (100 mg) and DMF (1 mL) was added potassium tert-butoxide (75 mg) at room temperature, followed by stirring for 5 minutes. To the reaction mixture was added 4-(bromomethyl)benzonitrile (131 mg), followed by stirring at room temperature for 2 hours. Water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine in this order, and dried over anhydrous sodium sulfate, and then the solvent was evaporated to obtain crude methyl 1-(4-cyanobenzyl)-1H-indole-7-carboxylate (211 mg). To a mixture of crude methyl 1-(4-cyanobenzyl)-1H-indole-7-carboxylate (211 mg), THF (10 mL), and methanol (5 mL) was added a 1 M aqueous sodium hydroxide solution (2.5 mL), and the obtained mixed liquid was stirred at 60° C. overnight. After leaving to be cooled to room temperature, the solvent was evaporated under reduced pressure, and to the obtained residue was added ethyl acetate, followed by extraction with water. The aqueous layer was neutralized by adding 1 M hydrochloric acid (2.5 mL), and extracted with ethyl acetate. This organic layer was dried over anhydrous sodium sulfate, and then the solvent was evaporated to obtain crude 1-(4-carbamoylbenzyl)-1H-indole-7-carboxylic acid (230 mg). To a mixture of crude 1-(4-carbamoylbenzyl)-1H-indole-7-carboxylic acid (229 mg), methyl (S)-4-[1-aminoethyl]benzoate hydrochloride (123 mg), and HOBt (23 mg) in DMF (3 mL) was added EDCI.HCl (150 μL), followed by stirring at room temperature for 3 hours. Water was added thereto, followed by extraction with ethyl acetate-diethyl ether. The organic layer was washed with water and saturated brine in this order, and dried over anhydrous sodium sulfate. After evaporating the solvent, to the obtained residue was added methanol. The precipitated solid was collected by filtration and dried to obtain methyl (S)-4-[1-({[1-(4-carbamoylbenzyl)-1H-indol-7-yl]carbonyl}amino)ethyl]benzoate (142 mg).

Workup

  1. stirringby stirring at room temperature for 2 hours
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with water and saturated brine in this order
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent was evaporated
  6. customto obtain crude methyl 1-(4-cyanobenzyl)-1H-indole-7-carboxylate (211 mg)
  7. additionthe obtained mixed liquid
  8. stirringwas stirred at 60° C. overnight
  9. customAfter leaving
  10. customthe solvent was evaporated under reduced pressure
  11. additionto the obtained residue was added ethyl acetate
  12. extractionfollowed by extraction with water
  13. additionby adding 1 M hydrochloric acid (2.5 mL)
  14. extractionextracted with ethyl acetate
  15. dry with materialThis organic layer was dried over anhydrous sodium sulfate
  16. customthe solvent was evaporated
  17. customto obtain crude 1-(4-carbamoylbenzyl)-1H-indole-7-carboxylic acid (230 mg)
  18. stirringby stirring at room temperature for 3 hours
  19. extractionfollowed by extraction with ethyl acetate-diethyl ether
  20. washThe organic layer was washed with water and saturated brine in this order
  21. dry with materialdried over anhydrous sodium sulfate
  22. customAfter evaporating the solvent
  23. additionto the obtained residue was added methanol
  24. filtrationThe precipitated solid was collected by filtration
  25. customdried

Sources & evidence

ORD record
ord-ac66feeb2f274bb385c617c5c8f1698a
Source dataset
uspto-grants-2013_12
Patent number
US08598355B2

Reaction notes

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