1,4-Cyclohexadiene → HCID 71253729, compound

HRID 1775057Notes

Reaction equation

HRID 1775057 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[C:9]3[C:15]([C:16]4[N:21]=[C:20]([N:22]5[CH2:28][CH2:27][CH2:26][C@@H:25]([NH:29]C(=O)OCC6C=CC=CC=6)[CH2:24][CH2:23]5)[CH:19]=[CH:18][CH:17]=4)=[N:14][N:13]([CH:40]4[CH2:45][CH2:44][CH2:43][CH2:42][O:41]4)[C:10]3=[CH:11][N:12]=2)[CH:4]=[N:3]1.C1CC=CCC=1>C(O)C.[Pd]>[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[C:9]3[C:15]([C:16]4[N:21]=[C:20]([N:22]5[CH2:28][CH2:27][CH2:26][C@@H:25]([NH2:29])[CH2:24][CH2:23]5)[CH:19]=[CH:18][CH:17]=4)=[N:14][N:13]([CH:40]4[CH2:45][CH2:44][CH2:43][CH2:42][O:41]4)[C:10]3=[CH:11][N:12]=2)[CH:4]=[N:3]1

Participants

5

Reactant 2

HCID 123431,4-CyclohexadieneHCID 86676692HCID 86676692, compound

Product 1

HCID 71253729HCID 71253729, compoundYield 71.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

In a 5-mL high-pressure vial was placed benzyl (4R)-1-(6-(5-(1-methyl-1H-pyrazol-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)azepan-4-ylcarbamate (110.0 mg, 0.18 mmol), 1,4-cyclohexadiene (102 μL, 1.09 mmol) in ethanol (8.3). 10% Pd on C (11.0 mg) was added, and the reaction mixture was vacuum purged with N2 3×. The vial was sealed and the reaction mixture was stirred at 100° C. After 2 h additional 10% Pd on C (11.0 mg) and 1,4-cyclohexadiene (102 μL) were added. The vial was resealed and the reaction mixture was stirred at 100° C. for 14 h. The cooled reaction was filtered reaction through a pad of Celite®, and the pad was rinsed with EtOAc (3×5 mL), MeOH (3×5 mL), DCM (3×5 mL), and a final rinse of EtOAc (3×5 mL). The filtrate was concentrated under reduced pressure, and the crude product was purified using flash chromatography (Si-PPC gradient elution, solvent: 0-80% MeOH in EtOAc+1% Et3N) to give (4R)-1-(6-(5-(1-methyl-1H-pyrazol-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)azepan-4-amine as a solid (61.1 mg, 71.3%). LC/MS: m/z 473.3 [M+1].

Workup

  1. custompurged with N2 3×
  2. customThe vial was sealed
  3. additionAfter 2 h additional 10% Pd on C (11.0 mg) and 1,4-cyclohexadiene (102 μL) were added
  4. stirringthe reaction mixture was stirred at 100° C. for 14 h
  5. customThe cooled reaction
  6. filtrationwas filtered
  7. customreaction through a pad of Celite®
  8. washthe pad was rinsed with EtOAc (3×5 mL), MeOH (3×5 mL), DCM (3×5 mL)
  9. washa final rinse of EtOAc (3×5 mL)
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customthe crude product was purified
  12. washflash chromatography (Si-PPC gradient elution, solvent: 0-80% MeOH in EtOAc+1% Et3N)

Sources & evidence

ORD record
ord-f708f42b2d3b4c8c9d0f5787eafeba78
Source dataset
uspto-grants-2016_02
Patent number
US09260425B2

Reaction notes

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