1,4-Cyclohexadiene → HCID 58464790, compound

HRID 2089430Notes

Reaction equation

HRID 2089430 reaction equation
[NH2:1][C:2]1[C:3]([C:9]([NH:11][C:12]2[CH:13]=[N:14][N:15]([CH3:35])[C:16]=2[N:17]2[CH2:23][CH2:22][CH2:21][C@@H:20]([NH:24]C(=O)OCC3C=CC=CC=3)[CH2:19][CH2:18]2)=[O:10])=[N:4][C:5](Cl)=[N:6][CH:7]=1.C1CC=CCC=1>[Pd].C(O)C>[NH2:1][C:2]1[C:3]([C:9]([NH:11][C:12]2[CH:13]=[N:14][N:15]([CH3:35])[C:16]=2[N:17]2[CH2:23][CH2:22][CH2:21][C@@H:20]([NH2:24])[CH2:19][CH2:18]2)=[O:10])=[N:4][CH:5]=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 123431,4-CyclohexadieneHCID 58464830HCID 58464830, compound

Product 1

HCID 58464790HCID 58464790, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
95 °C

Procedure

In a 40 mL sealed vial was added (R)-benzyl 1-(4-(5-amino-2-chloropyrimidine-4-carboxamido)-1-methyl-1H-pyrazol-5-yl)azepan-4-ylcarbamate (140 mg, 0.28 mmol), 1,4-cyclohexadiene (0.16 mL, 1.68 mmol) and ethanol (12 mL). 10% Pd/C (30 mg, 0.028 mmol) was added and the reaction vial was vacuum purged with nitrogen three times. The reaction mixture was then stirred at 95° C. under nitrogen for 2 h. LCMS indicated de-chlorinated product as the malor product. After cooling down to room temperature, the reaction mixture was filtered through Celite and rinsed thoroughly with methanol. The solvent was distilled off under reduced pressure to give the crude product which was purified via reverse phase HPLC to afford 326. 1H NMR (400 MHz, DMSO) δ 8.48 (s, 1H), 8.46 (s, 1H), 7.51 (s, 1H), 6.88 (s, 3H), 3.65 (s, 4H), 3.19-2.89 (m, 9H), 1.93-1.69 (m, 4H), 1.69-1.41 (m, 4H). MS (ESI) m/z: 331.2 [M+H+].

Workup

  1. customIn a 40 mL sealed vial
  2. custompurged with nitrogen three times
  3. temperatureAfter cooling down to room temperature
  4. filtrationthe reaction mixture was filtered through Celite
  5. washrinsed thoroughly with methanol
  6. distillationThe solvent was distilled off under reduced pressure
  7. customto give the crude product which
  8. customwas purified via reverse phase HPLC

Sources & evidence

ORD record
ord-6199c68249e0436ba925f56f316a60d2
Source dataset
uspto-grants-2013_05
Patent number
US08436001B2

Reaction notes

Loading…