Potassium Carbonate → HCID 11582026, compound

HRID 600658Notes

Reaction equation

HRID 600658 reaction equation
[CH3:1][N:2]1[CH:7]2[CH2:8][CH2:9][CH:3]1[CH2:4][CH:5]([NH:10][C:11]([C:13]1[C:21]3[C:16](=[CH:17][CH:18]=[C:19](Br)[CH:20]=3)[NH:15][N:14]=1)=[O:12])[CH2:6]2.[O:23]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24]1.F[B-](F)(F)F.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(=O)([O-])[O-].[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[O:23]1[CH:27]=[CH:26][C:25]([C:19]2[CH:20]=[C:21]3[C:16](=[CH:17][CH:18]=2)[NH:15][N:14]=[C:13]3[C:11]([NH:10][CH:5]2[CH2:4][CH:3]3[N:2]([CH3:1])[CH:7]([CH2:8][CH2:9]3)[CH2:6]2)=[O:12])=[CH:24]1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 2734358Furan-3-boronic acidHCID 44558591Tri-t-butylphosphine fluoroborateHCID 57560955HCID 57560955, compound

Product 1

HCID 11582026HCID 11582026, compoundYield 4%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

In a 5 mL microwave reaction vessel was added N-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-5-bromo-1H-indazole-3-carboxamide (0.286 mmol), furan-3-boronic acid (0.588 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.0289 mmol), tri-tert-butylphosphine tetrafluoroborate (0.0579 mmol), and potassium carbonate (0.810 mmol). The vessel was evacuated, back-filled with argon gas, and the contents diluted with N,N-dimethylformamide (5.0 mL). The vessel was sealed and subjected to microwave irradiation at 200° C. for 600 s. The contents of the reaction were filtered through Celite (methanol wash) and loaded on a 5 g SCX column. The column was washed with methanol (50 mL) and the product was eluted with 2 M ammonia in methanol and concentrated. The residue was purified by chromatography [1/1 to 0/1 ethyl acetate/(70/30/1 ethyl acetate/methanol/ammonium hydroxide)] followed by preparative HPLC, thus providing the product in 4% yield. 1H NMR (CD3OD) δ 8.51 (s, 1H), 8.35 (s, 1H), 7.93 (s, 1H), 7.70-7.58 (m, 3H), 6.87 (s, 1H), 4.56-4.52 (m, 0.5H), 4.28-4.26 (m, 0.5H), 3.97-3.93 (m, 2H), 2.84 (s, 3H), 2.49-2.12 (m, 8H); LC/MS (EI) tR 4.20 min, m/z 351 (M++1).

Workup

  1. customThe vessel was evacuated
  2. additionback-filled with argon gas
  3. additionthe contents diluted with N,N-dimethylformamide (5.0 mL)
  4. customThe vessel was sealed
  5. customirradiation at 200° C. for 600 s
  6. filtrationThe contents of the reaction were filtered through Celite (methanol wash)
  7. washThe column was washed with methanol (50 mL)
  8. washthe product was eluted with 2 M ammonia in methanol
  9. concentrationconcentrated
  10. customThe residue was purified by chromatography [1/1 to 0/1 ethyl acetate/(70/30/1 ethyl acetate/methanol/ammonium hydroxide)]
  11. customthus providing the product in 4% yield

Sources & evidence

ORD record
ord-46c8dd8077964efbb41048c6d47a3ea8
Source dataset
uspto-grants-2011_03
Patent number
US07902217B2

Reaction notes

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