Ethylenediamine → 2-(5-(5-(aminomethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-ylamino)-3-methyl-N-(2,2,2-trifluoroethyl)butanamide

HRID 510217Notes

Reaction equation

HRID 510217 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]2[C:11]([C:12]3[CH:13]=[C:14]([NH:18][CH:19]([CH:28]([CH3:30])[CH3:29])[C:20]([NH:22][CH2:23][C:24]([F:27])([F:26])[F:25])=[O:21])[CH:15]=[N:16][CH:17]=3)=[CH:10][N:9](COCC[Si](C)(C)C)[C:6]2=[N:7][CH:8]=1.C(O)(C(F)(F)F)=O.[OH-].[Na+].C(N)CN>ClCCl>[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]2[C:11]([C:12]3[CH:13]=[C:14]([NH:18][CH:19]([CH:28]([CH3:30])[CH3:29])[C:20]([NH:22][CH2:23][C:24]([F:25])([F:26])[F:27])=[O:21])[CH:15]=[N:16][CH:17]=3)=[CH:10][NH:9][C:6]2=[N:7][CH:8]=1

Participants

6

Reactant 4

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acid2×HCID 14798Sodium HydroxideHCID 1317332642-(5-(5-(aminomethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3 b]pyridin-3-yl)pyridin-3-ylamino)-3-methyl-N-(2,2,2-trifluoroethyl)butanamide

Product 1

HCID 894954382-(5-(5-(aminomethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-ylamino)-3-methyl-N-(2,2,2-trifluoroethyl)butanamideYield 91.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 2-(5-(5-(aminomethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-ylamino)-3-methyl-N-(2,2,2-trifluoroethyl)butanamide 10-1b (211 mg, 0.364 mmol) dissolved in dichlormethane (2.0 ml) was added TFA (2.0 ml, 26.0 mmol). The reaction stirred at room temp for 1.5 hrs, concentrated and the residue dissolved in MeOH (2.0 ml). NaOH (0.255 ml, 2.55 mmol) and ethylenediamine (0.049 ml, 0.728 mmol) were added and the reaction stirred for 2 hrs at room temperature. The reaction was then acidified with trifluoroacetic acid, filtered and purified by RP-HPLC (water:acetonitrile w/0.1% TFA, C-18, 15-50%). The pure fractions concentrated to remove acetonitrile and mixture neutralized with saturated sodium bicarbonate. The product was extracted with ethyl acetate (3×10 mL). The combined organics were then washed with brine, dried with sodium sulfate, filtered and concentrated to afford the product 10-1c (140 mg, 89%).

Workup

  1. concentrationconcentrated
  2. dissolutionthe residue dissolved in MeOH (2.0 ml)
  3. stirringthe reaction stirred for 2 hrs at room temperature
  4. filtrationfiltered
  5. custompurified by RP-HPLC (water:acetonitrile w/0.1% TFA, C-18, 15-50%)
  6. concentrationThe pure fractions concentrated
  7. customto remove acetonitrile and mixture
  8. extractionThe product was extracted with ethyl acetate (3×10 mL)
  9. washThe combined organics were then washed with brine
  10. dry with materialdried with sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-ea8996a58be04d7b819470706e4c9487
Source dataset
uspto-grants-2015_08
Patent number
US09096598B2

Reaction notes

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