5-Bromonicotinamide → HCID 135983723, compound

HRID 901499Notes

Reaction equation

HRID 901499 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[C:17]([C:18]4[N:19](S(C5C=CC(C)=CC=5)(=O)=O)[N:20]=[CH:21][CH:22]=4)=[CH:16][N:15](S(C4C=CC(C)=CC=4)(=O)=O)[C:12]3=[N:13][CH:14]=2)O1.Br[C:45]1[CH:46]=[N:47][CH:48]=[C:49]([CH:53]=1)[C:50]([NH2:52])=[O:51].ClCCl>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].C(#N)C>[N:20]1[NH:19][C:18]([C:17]2[C:11]3[C:12](=[N:13][CH:14]=[C:9]([C:45]4[CH:46]=[N:47][CH:48]=[C:49]([CH:53]=4)[C:50]([NH2:52])=[O:51])[CH:10]=3)[NH:15][CH:16]=2)=[CH:22][CH:21]=1

Participants

6

Reactant 3

HCID 18085-BromonicotinamideHCID 6344DichloromethaneHCID 59699799HCID 59699799, compound

Product 1

HCID 135983723HCID 135983723, compoundYield 3%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(toluene-4-sulfonyl)-3-[2-(toluene-4-sulfonyl)-2H-pyrazol-3-yl]-1H-pyrrolo[2,3-b]pyridine (56 mg, 0.09 mmol) in a 1:1 acetonitrile/saturated aqueous NaHCO3 solution (2 mL total) in a microwave vial was added 5-bromonicotinamide (20 mg, 0.10 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II), complex with dichloromethane (1:1) (3.7 mg, 0.004 mmol). The vial was capped, flushed with N2, evacuated under vacuum, and heated in a microwave at 90° C. for 1800 seconds. The product was extracted into ethyl acetate and the organic layer was dried over Na2SO4. The solution was filtered and concentrated under vacuum. The residue was redissolved in a 1:1 MeOH/acetone solution (2 mL total) and treated with 200 uL of 50% KOH (aq) solution and stirred at ambient temperature for 1 hour. Citric acid (1 M) was added dropwise until pH=7 and the product was extracted into ethyl acetate. The organic layer was dried over Na2SO4, filtered, and adsorbed onto silica gel. The material was purified by flash chromatography using a gradient of ethyl acetate (containing 10% MeOH) and hexane then concentrated under vacuum. The residue was titrated with diethyl ether to afford the title compound as a beige solid (0.8 mg, 3% yield). 1H NMR (500 MHz, d6-DMSO) δ 12.67 (s, 1H), 11.87 (s, 1H), 8.95 (s, 1H), 8.62 (s, 1H), 8.50 (s, 1H), 8.25 (s, 1H), 7.89 (s, 1H), 7.63 (s, 1H), 7.41 (d, J=7.5 Hz, 1H), 7.05 (d, J=7.5 Hz, 1H). MS: m/z 305.0 (M+H+).

Workup

  1. customThe vial was capped
  2. customflushed with N2
  3. customevacuated under vacuum
  4. extractionThe product was extracted into ethyl acetate
  5. dry with materialthe organic layer was dried over Na2SO4
  6. filtrationThe solution was filtered
  7. concentrationconcentrated under vacuum
  8. dissolutionThe residue was redissolved in a 1:1 MeOH/acetone solution (2 mL total)
  9. additiontreated with 200 uL of 50% KOH (aq) solution
  10. additionCitric acid (1 M) was added dropwise until pH=7
  11. extractionthe product was extracted into ethyl acetate
  12. dry with materialThe organic layer was dried over Na2SO4
  13. filtrationfiltered
  14. customThe material was purified by flash chromatography
  15. concentrationthen concentrated under vacuum

Sources & evidence

ORD record
ord-894f0bc70a704c959a061c700f3e7ac5
Source dataset
uspto-grants-2008_04
Patent number
US07361764B2

Reaction notes

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