Triethylamine → 4-({5-[(2-ethoxy-2-oxoethyl)carbamoyl]adamantan-2-yl}amino)-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid

HRID 1360180Notes

Reaction equation

HRID 1360180 reaction equation
Cl[C:2]1[C:7]([C:8]([O:10]CC2C=CC=CC=2)=[O:9])=[CH:6][N:5]=[C:4]2[NH:18][CH:19]=[CH:20][C:3]=12.[NH2:21][CH:22]1[CH:29]2[CH2:30][C:25]3([C:32]([NH:34][CH2:35][C:36]([O:38][CH2:39][CH3:40])=[O:37])=[O:33])[CH2:26][CH:27]([CH2:31][CH:23]1[CH2:24]3)[CH2:28]2.C(N(CC)CC)C.C(OCC)(=O)C>CN1CCCC1=O.O>[CH2:39]([O:38][C:36](=[O:37])[CH2:35][NH:34][C:32]([C:25]12[CH2:30][CH:29]3[CH2:28][CH:27]([CH2:31][CH:23]([CH:22]3[NH:21][C:2]3[C:7]([C:8]([OH:10])=[O:9])=[CH:6][N:5]=[C:4]4[NH:18][CH:19]=[CH:20][C:3]=34)[CH2:24]1)[CH2:26]2)=[O:33])[CH3:40]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 57928592benzyl 4-chloro-1H-pyrrolo[2,3-b]pyridine-5-carboxylateHCID 57928760Ethyl {[(4-amino-1-adamantyl)carbonyl]amino}acetate

Product 1

HCID 579282594-({5-[(2-ethoxy-2-oxoethyl)carbamoyl]adamantan-2-yl}amino)-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acidYield 21.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
180 °C

Procedure

Benzyl 4-chloro-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (55 mg), ethyl {[(4-amino-1-adamantyl) carbonyl]amino}acetate (54 mg) and triethylamine (80 μl) were dissolved in N-methyl-2-pyrrolidone (0.55 ml) and stirred at 180° C. for 1 hour using a microwave reaction system. To the reaction solution were added ethyl acetate and water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate), the obtained compound was dissolved in dioxane (1.1 ml) and methanol (1.1 ml), 10% palladium on carbon (50% wet) was added, and catalytic reduction was performed for 4 hours at ambient temperature at 1 atm. Methanol, dioxane, and 1M hydrochloric acid were added, and the precipitated solid was dissolved and filtered to remove the catalyst. The filtrate was concentrated under reduced pressure to obtain 4-({5-[(2-ethoxy-2-oxoethyl)carbamoyl]adamantan-2-yl}amino)-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid (18 mg).

Workup

  1. customa microwave reaction system
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over magnesium sulfate
  5. customevaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate)
  7. dissolutionthe obtained compound was dissolved in dioxane (1.1 ml)
  8. additionmethanol (1.1 ml), 10% palladium on carbon (50% wet) was added
  9. waitcatalytic reduction was performed for 4 hours at ambient temperature at 1 atm
  10. additionMethanol, dioxane, and 1M hydrochloric acid were added
  11. dissolutionthe precipitated solid was dissolved
  12. filtrationfiltered
  13. customto remove the catalyst
  14. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-07b212e837e74cb4807e3c4f89ed74a2
Source dataset
uspto-grants-2011_02
Patent number
US07879844B2

Reaction notes

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