Nitrogen → Tert-butyl 4-{4-amino-5-[3-fluoro-4-({[2-fluoro-5-(trifluoromethyl)phenyl]carbamoyl}amino)phenyl]-6-(methoxymethyl)pyrrolo[2,1-f][1,2,4]triazin-7-yl}piperidine-1-carboxylate

HRID 73718Notes

Reaction equation

HRID 73718 reaction equation
N#N.[NH2:3][C:4]1[C:9]2=[C:10]([C:29]3[CH:34]=[CH:33][C:32]([NH:35][C:36](=[O:49])[NH:37][C:38]4[CH:43]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:41]=[CH:40][C:39]=4[F:48])=[C:31]([F:50])[CH:30]=3)[C:11]([CH2:26][O:27][CH3:28])=[C:12]([C:13]3[CH2:14][CH2:15][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:17][CH:18]=3)[N:8]2[N:7]=[CH:6][N:5]=1>[Pt]=O.C(O)(=O)C>[NH2:3][C:4]1[C:9]2=[C:10]([C:29]3[CH:34]=[CH:33][C:32]([NH:35][C:36](=[O:49])[NH:37][C:38]4[CH:43]=[C:42]([C:44]([F:47])([F:45])[F:46])[CH:41]=[CH:40][C:39]=4[F:48])=[C:31]([F:50])[CH:30]=3)[C:11]([CH2:26][O:27][CH3:28])=[C:12]([CH:13]3[CH2:14][CH2:15][N:16]([C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])[CH2:17][CH2:18]3)[N:8]2[N:7]=[CH:6][N:5]=1

Participants

5

Reactant 2

HCID 947NitrogenHCID 57955356HCID 57955356, compound

Product 1

HCID 66641290Tert-butyl 4-{4-amino-5-[3-fluoro-4-({[2-fluoro-5-(trifluoromethyl)phenyl]carbamoyl}amino)phenyl]-6-(methoxymethyl)pyrrolo[2,1-f][1,2,4]triazin-7-yl}piperidine-1-carboxylateYield 75.3%

Reagents, catalysts & solvents 2

HCID 82844Platinum oxide (PtO)CatalystHCID 176Acetic AcidSolvent

Procedure

To a flask charged with N2 was added tert-butyl 4-{4-amino-5-[3-fluoro-4-({[2-fluoro-5-(trifluoromethyl)phenyl]carbamoyl}amino)phenyl]-6-(methoxymethyl)-pyrrolo-[2,1-f][1,2,4]triazin-7-yl}-3,6-dihydropyridine-1(2H)-carboxylate (424 mg, 0.629 mmol, 1.0 eq) followed by glacial acetic acid (40 mL). To this solution was added platinum oxide (42 mg, 10% w/w). The reaction solution was evacuated via vacuum and replaced with nitrogen (5×). The reaction mixture was then evacuated again via vacuum and placed under 1 atm of hydrogen and was allowed to stir for 17 hours. The solution was filtered through a pad of celite, washed with acetic acid and concentrated. The crude concentrate was dissolved in EtOAc and washed with saturated sodium bicarbonate. The organic layer was dried (Na2SO4), filtered, condensed, and purified via flash chromatography (1:1 tetrahydrofuran/hexanes). The purified fractions were collected, evaporated, and left under vacuum overnight to yield the title compound (320 mg, 75.3% yield). 1H-NMR (DMSO-d6) MS [M+H]+=676; LCMS RT=3.52 min.

Workup

  1. customThe reaction solution was evacuated via vacuum
  2. customThe reaction mixture was then evacuated again via vacuum
  3. filtrationThe solution was filtered through a pad of celite
  4. washwashed with acetic acid
  5. concentrationconcentrated
  6. concentrationThe crude concentrate
  7. dissolutionwas dissolved in EtOAc
  8. washwashed with saturated sodium bicarbonate
  9. dry with materialThe organic layer was dried (Na2SO4)
  10. filtrationfiltered
  11. customcondensed
  12. custompurified via flash chromatography (1:1 tetrahydrofuran/hexanes)
  13. customThe purified fractions were collected
  14. customevaporated
  15. waitleft under vacuum overnight

Sources & evidence

ORD record
ord-722b2033175c44a28e13c3bfd62c88ca
Source dataset
uspto-grants-2014_09
Patent number
US08829185B2

Reaction notes

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