2-(Dicyclohexylphosphino)biphenyl → HCID 58397894, compound

HRID 451563Notes

Reaction equation

HRID 451563 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[F:26][C:27]1([F:52])[CH:32]([NH:33][C:34]2[N:51]=[C:37]3[C:38]([C:42]4[CH:47]=[CH:46][C:45]([F:48])=[C:44]([F:49])[C:43]=4[F:50])=[CH:39][CH:40]=[CH:41][N:36]3[N:35]=2)[CH2:31][CH2:30][NH:29][CH2:28]1.Cl[C:54]1[S:58][N:57]=[C:56]([CH3:59])[N:55]=1.CC(C)([O-])C.[Na+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:52][C:27]1([F:26])[CH:32]([NH:33][C:34]2[N:51]=[C:37]3[C:38]([C:42]4[CH:47]=[CH:46][C:45]([F:48])=[C:44]([F:49])[C:43]=4[F:50])=[CH:39][CH:40]=[CH:41][N:36]3[N:35]=2)[CH2:31][CH2:30][N:29]([C:54]2[S:58][N:57]=[C:56]([CH3:59])[N:55]=2)[CH2:28]1

Participants

7

Reactant 4

HCID 27342162-(Dicyclohexylphosphino)biphenyl3×HCID 129191595-Chloro-3-methyl-1,2,4-thiadiazole3×HCID 23676156Sodium t-butoxideHCID 67343436N-(3,3-difluoropiperidin-4-yl)-8-(2,3,4-trifluorophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine

Product 1

HCID 58397894HCID 58397894, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalyst3×HCID 312751,4-DioxaneSolvent4×

Conditions

Temperature
150 °C

Procedure

A degassed solution of 2-(dicyclohexylphosphino)biphenyl (12.7 mg, 36.3 μmol) and palladium(II) acetate (4.08 mg, 18.2 μmol) in dioxane (2 mL) was stirred for 10 minutes at room temperature, then a solution of N-(3,3-difluoropiperidin-4-yl)-8-(2,3,4-trifluorophenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine (87 mg, 227 μmol), 5-chloro-3-methyl-1,2,4-thiadiazole (30.5 mg, 227 μmol) and sodium tert-butoxide (32.7 mg, 340 μmol) in dioxane (2 mL) was added. Through the solution was bubbled argon for 5 minutes, then heated to 150° C. in the microwave for 60 minutes. Again a degassed solution of 2-(dicyclohexylphosphino)biphenyl (12.7 mg, 36.3 μmol) and palladium(II) acetate (4.08 mg, 18.2 μmol) in dioxane (2 mL) was added, followed by 5-chloro-3-methyl-1,2,4-thiadiazole (30.5 mg, 227 μmol) and heated to 150° C. in the microwave for further 60 minutes. Again a degassed solution of 2-(dicyclohexylphosphino)biphenyl (12.7 mg, 36.3 μmol) and palladium(II) acetate (4.08 mg, 18.2 mmol) in dioxane (2 mL) was added, followed by 5-chloro-3-methyl-1,2,4-thiadiazole (30.5 mg, 227 μmol) and heated to 150° C. in the microwave for further 60 minutes. The crude material was purified by flash chromatography (silica gel, 70 g, 0% to 15% MeOH/NH4OH (9:1) in dichloromethane) and then by preparative HPLC. The title compound was obtained as white foam (42 mg, 38%).

Workup

  1. customThrough the solution was bubbled argon for 5 minutes
  2. temperatureheated to 150° C. in the microwave for further 60 minutes
  3. temperatureheated to 150° C. in the microwave for further 60 minutes
  4. customThe crude material was purified by flash chromatography (silica gel, 70 g, 0% to 15% MeOH/NH4OH (9:1) in dichloromethane)

Sources & evidence

ORD record
ord-588cd40cb4bf45cd8c5cd9b788548c6f
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

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