Phenyl N-(4-(1-(methylamino)carbonyl-1H-5-indolyloxy)-2-pyridyl)-N-(phenoxycarbonyl)carbamate → 5-(2-(((4-(3-Carbamoylpropyl)piperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-indole-1-carboxylic acid methylamide

HRID 2215524Notes

Reaction equation

HRID 2215524 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8][CH2:9][C:10]([NH2:12])=[O:11])[CH2:3][CH2:2]1.[CH3:13][NH:14][C:15]([N:17]1[C:25]2[C:20](=[CH:21][C:22]([O:26][C:27]3[CH:32]=[CH:31][N:30]=[C:29]([N:33](C(OC4C=CC=CC=4)=O)[C:34](=O)[O:35]C4C=CC=CC=4)[CH:28]=3)=[CH:23][CH:24]=2)[CH:19]=[CH:18]1)=[O:16]>CN(C)C=O>[CH3:13][NH:14][C:15]([N:17]1[C:25]2[C:20](=[CH:21][C:22]([O:26][C:27]3[CH:32]=[CH:31][N:30]=[C:29]([NH:33][C:34]([N:1]4[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8][CH2:9][C:10](=[O:11])[NH2:12])[CH2:3][CH2:2]4)=[O:35])[CH:28]=3)=[CH:23][CH:24]=2)[CH:19]=[CH:18]1)=[O:16]

Participants

4

Reactant 2

HCID 21949175Phenyl N-(4-(1-(methylamino)carbonyl-1H-5-indolyloxy)-2-pyridyl)-N-(phenoxycarbonyl)carbamateHCID 219492354-(Piperidin-4-yl)butanamide

Product 1

HCID 104351995-(2-(((4-(3-Carbamoylpropyl)piperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-indole-1-carboxylic acid methylamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(Piperidin-4-yl)butanamide (547 mg, 1.41 mmol) was dissolved in N,N-dimethylformamide (3 ml); phenyl N-(4-(1-(methylamino)carbonyl-1H-indol-5-yloxy)-pyridin-2-yl)-N-(phenoxycarbonyl)carbamate (210 mg, 0.402 mmol, the product of Production example 5-2) was added thereto; and the reaction mixture was stirred at room temperature for 1.5 hour. The reaction mixture was partitioned between ethyl acetate and water; the organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure; and the residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate-methanol system). The obtained amorphous solid was crystallized by adding diethyl ether. After addition of a small amount of ethanol to make a suspension, this was diluted with hexane. After separation by filtration to obtain crystals, these were rinsed with diethyl ether and dried under aeration. Thus, the title compound was obtained as colorless crystals (157 mg, 0.328 mmol, 81.7%).

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and water
  2. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customand the residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate-methanol system)
  5. customThe obtained amorphous solid was crystallized
  6. additionby adding diethyl ether
  7. additionAfter addition of a small amount of ethanol
  8. additionthis was diluted with hexane
  9. customAfter separation
  10. filtrationby filtration
  11. customto obtain crystals
  12. washthese were rinsed with diethyl ether
  13. customdried under aeration

Sources & evidence

ORD record
ord-c8f1507c1f4a44a19ae2ccb01783a1d8
Source dataset
uspto-grants-2006_09
Patent number
US07109219B2

Reaction notes

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