Dimethylformamide → ((4-(1-ethylcarbamoyl-1H-indol-5-yloxy)pyridin-2-yl)aminocarbonylamino)acetic acid

HRID 2215535Notes

Reaction equation

HRID 2215535 reaction equation
Cl.[NH2:2][CH2:3][C:4]([O:6]C)=[O:5].CN(C)C=O.[CH2:13]([NH:15][C:16]([N:18]1[C:26]2[C:21](=[CH:22][C:23]([O:27][C:28]3[CH:33]=[CH:32][N:31]=[C:30]([N:34](C(OC4C=CC=CC=4)=O)[C:35](=O)[O:36]C4C=CC=CC=4)[CH:29]=3)=[CH:24][CH:25]=2)[CH:20]=[CH:19]1)=[O:17])[CH3:14]>C(N(CC)CC)C>[CH2:13]([NH:15][C:16]([N:18]1[C:26]2[C:21](=[CH:22][C:23]([O:27][C:28]3[CH:33]=[CH:32][N:31]=[C:30]([NH:34][C:35]([NH:2][CH2:3][C:4]([OH:6])=[O:5])=[O:36])[CH:29]=3)=[CH:24][CH:25]=2)[CH:20]=[CH:19]1)=[O:17])[CH3:14]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 122755Glycine methyl ester hydrochlorideHCID 21949095Phenyl N-(4-(1-(ethylamino)carbonyl-1H-5-indolyloxy)-2-pyridyl)-N-(phenoxycarbonyl)carbamate

Product 1

HCID 21949268((4-(1-ethylcarbamoyl-1H-indol-5-yloxy)pyridin-2-yl)aminocarbonylamino)acetic acidYield 80.5%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

Methyl aminoacetate hydrochloride (292 mg, 2.33 mmol) was suspended in a solvent mixture of N,N-dimethylformamide (4 ml) and triethylamine (1 ml); phenyl N-(4-(1-(ethylamino)carbonyl-1H-5-indolyloxy)-2-pyridyl)-N-(phenoxycarbonyl)carbamate (250 mg, 0.466 mmol, Production example 55-1) was added thereto; and the reaction mixture was stirred at room temperature for 2 days. The reaction mixture was partitioned between ethyl acetate and water; and the organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was dissolved in a solvent mixture of tetrahydrofuran (2 ml) and methanol (1 ml); and 4N aqueous solution of sodium hydroxide was added thereto while stirred at room temperature; and the reaction mixture was stirred for 1.5 hour at room temperature. After 1N hydrochloric acid was added, extraction was performed with ethyl acetate-tetrahydrofuran, washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained crystals were suspended in diethyl ether, filtered off, washed with dimethyl ether, and dried under aeration to yield the title compound as colorless crystals (149 mg, 0.375 mmol, 80.5%).

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and water
  2. washand the organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe obtained residue was dissolved in a solvent mixture of tetrahydrofuran (2 ml) and methanol (1 ml)
  6. additionand 4N aqueous solution of sodium hydroxide was added
  7. stirringwhile stirred at room temperature
  8. stirringand the reaction mixture was stirred for 1.5 hour at room temperature
  9. additionAfter 1N hydrochloric acid was added
  10. extractionextraction
  11. washwashed with brine
  12. dry with materialdried over anhydrous sodium sulfate
  13. concentrationconcentrated under reduced pressure
  14. filtrationfiltered off
  15. washwashed with dimethyl ether
  16. customdried under aeration

Sources & evidence

ORD record
ord-c03b891b95074fa6b94c82fd0d74ad34
Source dataset
uspto-grants-2006_09
Patent number
US07109219B2

Reaction notes

Loading…