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

HRID 510216Notes

Reaction equation

HRID 510216 reaction equation
[C:1]([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]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:6]2=[N:7][CH:8]=1)#[N:2].CC(C)[C@@H](NC1C=NC=C(C2C3C(=NC=C(COCCN4CCCC4)C=3)N(COCC[Si](C)(C)C)C=2)C=1)C(NCC(F)(F)F)=O>C(O)C.[Ni]>[NH2:2][CH2:1][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]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:6]2=[N:7][CH:8]=1

Participants

5

Reactant 2

HCID 894955712-(5-(5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-ylamino)-3-methyl-N-(2,2,2-trifluoroethyl)butanamideHCID 89495580(R)-3-methyl-2-(5-(5-((2-(pyrrolidin-1-yl)ethoxy)methyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-ylamino)-N-(2,2,2-trifluoroethyl)butanamide

Product 1

HCID 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)butanamideYield 47%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 702EthanolSolvent

Procedure

To a solution of the 2-(5-(5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-ylamino)-3-methyl-N-(2,2,2-trifluoroethyl)butanamide, (9-1a) (110 mg, 187 mmol) 10-1a in ethanol (5.0 ml) was added Raney Nickel (2.197 mg, 0.037 mmol) Ammonium hydroxide (0.260 μl, 1.871 μmol) was added and the flask evacuated and backfilled with hydrogen gas 3 times. The mixture was stirred under hydrogen for 17 hrs. The reaction was purged with nitrogen, diluted with ethanol and filtered through a pad of celite. The filtrate was concentrated and oil purified by Reverse phase HPLC (Water:ACN w/0.1% TFA, C-18, 35-65% gradient). The pure fractions concentrated to remove acetonitrile and mixture neutralized with saturated sodium bicarbonate. The product was extracted with ethyl acetate (3×20 mL). The organics were dried with sodium sulfate, filtered and concentrated to afford the product 10-1b as a solid (50 mg, 47%).

Workup

  1. additionwas added
  2. customthe flask evacuated
  3. customThe reaction was purged with nitrogen
  4. additiondiluted with ethanol
  5. filtrationfiltered through a pad of celite
  6. concentrationThe filtrate was concentrated
  7. customoil purified by Reverse phase HPLC (Water:ACN w/0.1% TFA, C-18, 35-65% gradient)
  8. concentrationThe pure fractions concentrated
  9. customto remove acetonitrile and mixture
  10. extractionThe product was extracted with ethyl acetate (3×20 mL)
  11. dry with materialThe organics were dried with sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-427b22d657b44f299e8a880812a7684d
Source dataset
uspto-grants-2015_08
Patent number
US09096598B2

Reaction notes

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