Sodium Carbonate → HCID 46220546, compound

HRID 2035702Notes

Reaction equation

HRID 2035702 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[N:10][N:11]([CH:13]3[CH2:19][CH2:18][C:17]4[CH:20]=[CH:21][CH:22]=[CH:23][C:16]=4[N:15]([CH2:24][C:25]([F:28])([F:27])[F:26])[C:14]3=[O:29])[CH:12]=2)=[CH:4][C:3]=1[O:30][CH3:31].[N:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:31][O:30][C:3]1[CH:4]=[C:5]([C:8]2[N:9]=[N:10][N:11]([CH:13]3[CH2:19][CH2:18][C:17]4[CH:20]=[CH:21][CH:22]=[CH:23][C:16]=4[N:15]([CH2:24][C:25]([F:28])([F:27])[F:26])[C:14]3=[O:29])[CH:12]=2)[CH:6]=[CH:7][C:2]=1[C:35]1[CH:36]=[CH:37][N:32]=[CH:33][CH:34]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 66683035HCID 66683035, compound

Product 1

HCID 46220546HCID 46220546, compoundYield 90.2%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

3-[4-(4-Iodo-3-methoxyphenyl)-1H-1,2,3-triazol-1-yl]-1-(2,2,2-trifluoroethyl)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one (300 mg, 0.553 mmol) was added to a 20-ml μwave vial along with 4-pyridyl boronic acid (136 mg, 1.106 mmol), PdCl2(dppf) (81 mg, 0.111 mmol), 2M sodium carbonate in water (553 μl, 1.106 mmol), water (1906 μl) and dioxane (8605 μl). The vial was sealed and μwaved at 100° C. for 10 minutes. The reaction mixture was filtered through a plug of Celite. The plug was washed with 100 ml of dioxane and the filtrates were combined and concentrated under reduced pressure. The contents of the flask were reconstituted in 100 ml of water and extracted with ˜100 ml of DCM twice. The organic layers were combined, passed through a phase separator cartridge, and concentrated under reduced pressure. The residue was dissolved in 6 ml of DMSO and purified by reverse phase chromatography (20-100 MeCN in water (half was injected with a TFA modifier, the remaining half was purified using a Formic Acid modifier). The pure fractions were pooled and concentrated under reduced pressure. The compound was dissolved in ˜300 ml of DCM and washed with NaHCO3 (3×150 ml). The organic layer was passed through a phase separator to remove water and concentrated under reduced pressure to afford 3-[4-(3-methoxy-4-pyridin-4-ylphenyl)-1H-1,2,3-triazol-1-yl]-1-(2,2,2-trifluoroethyl)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one (246 mg, 0.499 mmol, 90% yield) as an off white solid.

Workup

  1. customThe vial was sealed
  2. filtrationThe reaction mixture was filtered through a plug of Celite
  3. washThe plug was washed with 100 ml of dioxane
  4. concentrationconcentrated under reduced pressure
  5. extractionextracted with ˜100 ml of DCM twice
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe residue was dissolved in 6 ml of DMSO
  8. custompurified by reverse phase chromatography (20-100 MeCN in water (half
  9. customthe remaining half was purified
  10. concentrationconcentrated under reduced pressure
  11. dissolutionThe compound was dissolved in ˜300 ml of DCM
  12. washwashed with NaHCO3 (3×150 ml)
  13. customto remove water
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-3f1b36b843514db889dbb15a0edc8142
Source dataset
uspto-grants-2013_11
Patent number
US08575150B2

Reaction notes

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