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

HRID 2215504Notes

Reaction equation

HRID 2215504 reaction equation
Cl.[NH2:2][CH2:3][C:4]([O:6]C)=[O:5].C(N(CC)CC)C.[CH3:15][NH:16][C:17]([N:19]1[C:27]2[C:22](=[CH:23][C:24]([O:28][C:29]3[CH:34]=[CH:33][N:32]=[C:31]([N:35](C(OC4C=CC=CC=4)=O)[C:36](=O)[O:37]C4C=CC=CC=4)[CH:30]=3)=[CH:25][CH:26]=2)[CH:21]=[CH:20]1)=[O:18].O>CN(C)C=O.C(OCC)(=O)C.O1CCCC1>[CH3:15][NH:16][C:17]([N:19]1[C:27]2[C:22](=[CH:23][C:24]([O:28][C:29]3[CH:34]=[CH:33][N:32]=[C:31]([NH:35][C:36]([NH:2][CH2:3][C:4]([OH:6])=[O:5])=[O:37])[CH:30]=3)=[CH:25][CH:26]=2)[CH:21]=[CH:20]1)=[O:18]

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 122755Glycine methyl ester hydrochlorideHCID 21949175Phenyl N-(4-(1-(methylamino)carbonyl-1H-5-indolyloxy)-2-pyridyl)-N-(phenoxycarbonyl)carbamate

Product 1

HCID 21949209((4-(1-methylcarbamoyl-1H-indol-5-yloxy)pyridin-2-yl)aminocarbonylamino)acetic acidYield 79.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21939870Tetrahydrofuran ethyl acetateSolvent

Procedure

Methyl aminoacetate hydrochloride (300 mg, 2.3 mmol) was dissolved in N,N-dimethylformamide (4 ml), and then triethylamine (1 ml) was added. Phenyl N-(4-(1-(methylamino)carbonyl-1H-indol-5-yloxy)-2-pyridyl)-N-(phenoxycarbonyl)carbamate (250 mg, 0.48 mmol) synthesized in Production example 5-2 was added thereto. The reaction mixture was stirred at room temperature for 22 hours. After water was added to the reaction mixture, extraction was performed with a solvent mixture of ethyl acetate-tetrahydrofuran. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Fuji Silysia BW-300, ethyl acetate). The obtained pale yellow oil was dissolved in a solvent mixture of tetrahydrofuran (2 ml)-methanol (1 ml), then 4N aqueous solution of lithium hydroxide (0.48 ml) was added, and the reaction mixture was stirred at room temperature for 1 hour. After that, 1N hydrochloric acid (2 ml) was added, and this was subjected to extraction with ethyl acetate-tetrahydrofuran. The organic layer was washed with brine and dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to yield the title compound (145 mg, 0.38 mmol, 79%) as colorless crystals.

Workup

  1. additionwas added
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (Fuji Silysia BW-300, ethyl acetate)
  6. dissolutionThe obtained pale yellow oil was dissolved in a solvent mixture of tetrahydrofuran (2 ml)-methanol (1 ml)
  7. addition4N aqueous solution of lithium hydroxide (0.48 ml) was added
  8. stirringthe reaction mixture was stirred at room temperature for 1 hour
  9. additionAfter that, 1N hydrochloric acid (2 ml) was added
  10. extractionthis was subjected to extraction with ethyl acetate-tetrahydrofuran
  11. washThe organic layer was washed with brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ed49c114d52b4a69a0707279195e512a
Source dataset
uspto-grants-2006_09
Patent number
US07109219B2

Reaction notes

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