1,4-Cyclohexadiene → HCID 58464805, compound

HRID 1185311Notes

Reaction equation

HRID 1185311 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:14]([NH:16][C:17]2[CH:18]=[N:19][N:20]([CH3:40])[C:21]=2[N:22]2[CH2:28][CH2:27][CH2:26][C@@H:25]([NH:29]C(=O)OCC3C=CC=CC=3)[CH2:24][CH2:23]2)=[O:15])=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C1CC=CCC=1>[Pd].C(O)C>[NH2:29][C@@H:25]1[CH2:26][CH2:27][CH2:28][N:22]([C:21]2[N:20]([CH3:40])[N:19]=[CH:18][C:17]=2[NH:16][C:14](=[O:15])[C:5]2[CH:4]=[CH:3][C:2]([F:1])=[C:7]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[N:6]=2)[CH2:23][CH2:24]1

Participants

5

Reactant 2

HCID 123431,4-CyclohexadieneHCID 86658423HCID 86658423, compound

Product 1

HCID 58464805HCID 58464805, 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-fluoro-6-phenylpicolinamido)-1-methyl-1H-pyrazol-5-yl)azepan-4-ylcarbamate (62 mg, 0.11 mmol), 1,4-cyclohexadiene (0.11 mL, 1.14 mmol) and ethanol (7 mL). 10% Pd/C (18.2 mg, 0.017 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. 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 229. 1H NMR (400 MHz, DMSO) δ 8.40 (s, 1H), 8.18-7.98 (m, 4H), 7.68-7.48 (m, 3H), 3.68 (s, 3H), 3.25-3.03 (m, 5H), 2.02-1.75 (m, 3H), 1.74-1.51 (m, 3H). MS (ESI) m/z: 409.2 [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-5d4fb70435f9467a9da0ed64b003f6b1
Source dataset
uspto-grants-2014_03
Patent number
US08669361B2

Reaction notes

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