3-Bromopyridine → HCID 58188946, compound

HRID 1423247Notes

Reaction equation

HRID 1423247 reaction equation
CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=[CH:24][CH:23]=[CH:22][C:21]=2[N:26]([CH3:28])C)CCCCC1.[CH2:35]([C@@H:42]1[NH:47][CH2:46][CH2:45][N:44]([C:48]2[CH:56]=[C:55]3[C:51]([C:52]([CH2:61][CH3:62])=[N:53][N:54]3[CH:57]3[CH2:60][CH2:59][CH2:58]3)=[CH:50][CH:49]=2)[CH2:43]1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.BrC1C=NC=CC=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:35]([C@@H:42]1[N:47]([C:24]2[CH:28]=[N:26][CH:21]=[CH:22][CH:23]=2)[CH2:46][CH2:45][N:44]([C:48]2[CH:56]=[C:55]3[C:51]([C:52]([CH2:61][CH3:62])=[N:53][N:54]3[CH:57]3[CH2:58][CH2:59][CH2:60]3)=[CH:50][CH:49]=2)[CH2:43]1)[C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1

Participants

7

Reactant 4

HCID 122863-BromopyridineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 58189077HCID 58189077, compound

Product 1

HCID 58188946HCID 58188946, compoundYield 94.9%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Into a 40 mL septum-cap vial were added sodium tert-butoxide (68 mg, 0.71 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (28 mg, 0.07 mmol), and Pd2(dba)3 (0.03 mmol). The vial was sealed and evacuated/purged 5× with nitrogen. A solution of 6-((S)-3-benzyl-piperazin-1-yl)-1-cyclobutyl-3-ethyl-1H-indazole (185 mg, 0.49 mmol) and 3-bromopyridine (158 mg, 1.02 mmol) in 3 mL of toluene was added, and the reaction mixture was heated at 100° C. for 15 h. The reaction mixture was cooled, filtered, concentrated, and purified by silica gel flash chromatography with a 0-100% EtOAc/Hexanes gradient to afford the title compound as a tan solid (30 mg, 13%). LC/MS (Method B) 3.10 min, [M+1]+ 452.

Workup

  1. customInto a 40 mL septum-cap vial
  2. customThe vial was sealed
  3. customevacuated/purged 5× with nitrogen
  4. temperatureThe reaction mixture was cooled
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by silica gel flash chromatography with a 0-100% EtOAc/Hexanes gradient

Sources & evidence

ORD record
ord-b1aef90ee5454c7aba3cf456c23c6620
Source dataset
uspto-grants-2015_01
Patent number
US08927546B2

Reaction notes

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