Hydrochloric Acid → HCID 10297013, compound

HRID 1006285Notes

Reaction equation

HRID 1006285 reaction equation
C([O:3][C:4]([C:6]1[N:7]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([O:31][CH3:32])[CH:26]=2)[C:8]2[C:13]([C:14]=1[C:15]1[CH:23]=[CH:22][C:18]([C:19](O)=[O:20])=[CH:17][CH:16]=1)=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:5])C.C(Cl)(=O)C(Cl)=O.[CH:39]1([NH2:42])[CH2:41][CH2:40]1.[OH-].[Na+].Cl>CN(C)C=O.CO.O1CCCC1>[CH:39]1([NH:42][C:19]([C:18]2[CH:22]=[CH:23][C:15]([C:14]3[C:13]4[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=4)[N:7]([CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[C:27]([O:31][CH3:32])[CH:26]=4)[C:6]=3[C:4]([OH:3])=[O:5])=[CH:16][CH:17]=2)=[O:20])[CH2:41][CH2:40]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 65578Oxalyl chlorideHCID 69828CyclopropylamineHCID 22676837HCID 22676837, compound

Product 1

HCID 10297013HCID 10297013, compoundYield 51.2%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a 25 mL round-bottomed flask at rt was charged with 4-{2-(ethoxycarbonyl)-1-[(3-methoxyphenyl)methyl]indol-3-yl}benzoic acid (Example 98, 270 mg, 0.63 mmol), tetrahydrofuran (2 mL) and one drop of N,N-dimethylformamide. Oxalyl chloride (240 mg, 0.16 mL, 1.89 mmol) was added to the above mixture dropwise. After 1 hour, the reaction mixture was concentrated and re-dissolved in tetrahydrofuran (2 mL) and cyclopropylamine (359 mg, 6.3 mmol) was added. After 10 minutes at rt, aqueous sodium hydroxide (3 N) was added to the reaction mixture and enough methanol was added to make the mixture one phase. The resulting solution was refluxed for 1 hour before it was cooled to rt and acidified with hydrochloric acid (1N) and extracted with ethyl acetate (25 mL). The organic layer was washed with water, brine and dried over anydrous sodium sulfate. The solution was concentrated in vacuo to give a white solid which was triturated with diethyl ether to provide 3-[4-(N-cyclopropylcarbamoyl)phenyl]-1-[(3-methoxyphenyl)methyl]indole-2-carboxylic acid as a white solid (142 mg, 51%): mp 237° C.; MS (electrospray, MH+) calcd for C27H25N2O4 441, found 441; 1H NMR (DMSO-d6) δ 13.1 (br s, 1H), 8.48 (d, J=4.0 Hz, 1H), 7.88 (d, J=8.3 Hz, 2H), 7.62 (d, J=8.4 Hz, 1H), 7.50 (d, J=8.6 Hz, 2H), 7.46 (d, J=8.1 Hz, 1H), 7.30-7.37 (m, 1H), 7.12-7.22 (m, 2H), 6.79 (dd, J=8.2, 2.5 Hz, 1H), 6.69 (dd, 1H), 6.62 (d, J=7.6 Hz, 1H), 5.83 (s, 2H), 3.68 (s, 3H), 2.85-2.89 (m, 1H), 0.56-0.64 (m, 2H), 0.65-0.75 (m, 2H).

Workup

  1. concentrationthe reaction mixture was concentrated
  2. dissolutionre-dissolved in tetrahydrofuran (2 mL)
  3. waitAfter 10 minutes at rt
  4. additionwas added
  5. temperatureThe resulting solution was refluxed for 1 hour before it
  6. extractionextracted with ethyl acetate (25 mL)
  7. washThe organic layer was washed with water, brine
  8. dry with materialdried over anydrous sodium sulfate
  9. concentrationThe solution was concentrated in vacuo
  10. customto give a white solid which
  11. customwas triturated with diethyl ether

Sources & evidence

ORD record
ord-f2427b7fa5844e43816d1d571dcf0a79
Source dataset
uspto-grants-2004_09
Patent number
US06787651B2

Reaction notes

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