Nitrogen → HCID 57955356, compound

HRID 73717Notes

Reaction equation

HRID 73717 reaction equation
N#N.[NH2:3][C:4]1[C:9]2=[C:10]([C:17]3[CH:22]=[CH:21][C:20]([NH:23][C:24]([NH:26][C:27]4[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[CH:29][C:28]=4[F:37])=[O:25])=[C:19]([F:38])[CH:18]=3)[C:11]([CH2:14][O:15][CH3:16])=[C:12](Br)[N:8]2[N:7]=[CH:6][N:5]=1.[C:39]([O:43][C:44]([N:46]1[CH2:51][CH:50]=[C:49](B2OC(C)(C)C(C)(C)O2)[CH2:48][CH2:47]1)=[O:45])([CH3:42])([CH3:41])[CH3:40].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[NH2:3][C:4]1[C:9]2=[C:10]([C:17]3[CH:22]=[CH:21][C:20]([NH:23][C:24](=[O:25])[NH:26][C:27]4[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[CH:29][C:28]=4[F:37])=[C:19]([F:38])[CH:18]=3)[C:11]([CH2:14][O:15][CH3:16])=[C:12]([C:49]3[CH2:50][CH2:51][N:46]([C:44]([O:43][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:45])[CH2:47][CH:48]=3)[N:8]2[N:7]=[CH:6][N:5]=1

Participants

6

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 57955300HCID 57955300, compound

Product 1

HCID 57955356HCID 57955356, compoundYield 88.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a flask charged with N2 was added 1-{4-[4-amino-7-bromo-6-(methoxymethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea (Intermediate AAC, Step 1) (500 mg, 0.875 mmol, 1.0 eq) and tert-butyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (677 mg, 2.19 mmol, 2.5 eq) followed by 1,4-dioxane (5 mL). Nitrogen was bubbled through the solution for 15 min and then 2M Na2CO3 (6 eq) was added. Nitrogen again bubbled through solution for 15 minutes and [1,1′-Bis(dipheylphosphino)ferrocene] (143 mg, 0.2 eq) was added. N2 was bubbled through the solution for an additional 15 min and then the reaction was placed in a preheated 80° C. oil bath for 17 h. The reaction solution was allowed to cool to rt and was diluted with EtOAc and water. The organic layer was washed water and brine. The combined organic layers were dried (Na2SO4), filtered, condensed, and purified via flash column chromatography (1:1 tetrahydrofuran/hexanes). The purified fractions were collected, evaporated, and left under vacuum overnight to yield the title compound (520 mg, 88.2% yield). 1H-NMR (DMSO-d6) MS [M+H]+=674; LCMS RT=3.51 min.

Workup

  1. customNitrogen was bubbled through the solution for 15 min
  2. customNitrogen again bubbled through solution for 15 minutes
  3. addition[1,1′-Bis(dipheylphosphino)ferrocene] (143 mg, 0.2 eq) was added
  4. customN2 was bubbled through the solution for an additional 15 min
  5. customwas placed in a preheated 80° C.
  6. customfor 17 h
  7. additionwas diluted with EtOAc and water
  8. washThe organic layer was washed water and brine
  9. dry with materialThe combined organic layers were dried (Na2SO4)
  10. filtrationfiltered
  11. customcondensed
  12. custompurified via flash column chromatography (1:1 tetrahydrofuran/hexanes)
  13. customThe purified fractions were collected
  14. customevaporated

Sources & evidence

ORD record
ord-e6cfdd6bcffd4dbe9941fbf6449d42a6
Source dataset
uspto-grants-2014_09
Patent number
US08829185B2

Reaction notes

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