Triethylamine → 5-(2-(3-((1R)-1-Carbamoyl-2-phenylethyl)ureido)pyridin-4-yloxy)-1H-indole-1-carboxylic acid methylamide

HRID 2376819Notes

Reaction equation

HRID 2376819 reaction equation
[CH3:1][NH:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]([N:21](C(OC4C=CC=CC=4)=O)[C:22](=[O:30])OC4C=CC=CC=4)[CH:16]=3)=[CH:11][CH:12]=2)[CH:7]=[CH:6]1)=[O:4].C(N(CC)CC)C.Cl.[NH2:48][C@H:49]([CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)[C:50]([NH2:52])=[O:51]>CN(C)C=O>[CH3:1][NH:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]([NH:21][C:22]([NH:48][C@@H:49]([C:50](=[O:51])[NH2:52])[CH2:53][C:54]4[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=4)=[O:30])[CH:16]=3)=[CH:11][CH:12]=2)[CH:7]=[CH:6]1)=[O:4]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 21949175Phenyl N-(4-(1-(methylamino)carbonyl-1H-5-indolyloxy)-2-pyridyl)-N-(phenoxycarbonyl)carbamateHCID 56777394H-D-Phe-NH2 hcl

Product 1

HCID 103225715-(2-(3-((1R)-1-Carbamoyl-2-phenylethyl)ureido)pyridin-4-yloxy)-1H-indole-1-carboxylic acid methylamideYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Phenyl N-(4-(1-(methylamino)carbonyl-1H-5-indolyloxy)-2-pyridyl)-N-(phenoxycarbonyl)carbamate (104 mg, 0.200 mmol) and triethylamine (1 ml) were dissolved in N,N-dimethylformamide (3 ml), and (2R)-2-amino-3-phenylpropionamide hydrochloride (201 mg, 1.00 mmol) was added, and the reaction mixture was stirred for 18 hours. The reaction mixture was partitioned between ethyl acetate and the saturated aqueous solution of ammonium chloride. The organic layer was washed with water and brine, and was dried over anhydrous magnesium sulfate. The solvent was distilled off, and the residue was purified by silica gel column chromatography (eluent; ethyl acetate:methanol=50:1). The crystals were precipitated from a solvent mixture of ethyl acetate-hexane, filtered off, and dried under aeration to yield the title compound (77.2 mg, 0.152 mmol, 76%) as white crystals.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate
  2. washThe organic layer was washed with water and brine
  3. dry with materialwas dried over anhydrous magnesium sulfate
  4. distillationThe solvent was distilled off
  5. customthe residue was purified by silica gel column chromatography (eluent; ethyl acetate:methanol=50:1)
  6. customThe crystals were precipitated from a solvent mixture of ethyl acetate-hexane
  7. filtrationfiltered off
  8. customdried under aeration

Sources & evidence

ORD record
ord-741cfbb3e13e4f2fbd71be2a62c161f6
Source dataset
uspto-grants-2008_12
Patent number
US07468380B2

Reaction notes

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