Sodium Carbonate → HCID 54747876, compound

HRID 386756Notes

Reaction equation

HRID 386756 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:34]=[CH:35][CH:36]=1)[CH2:5][N:6]1[C:11](=[O:12])[C:10]([C:13]([NH:15][CH2:16][C:17]([O:19]C(C)(C)C)=[O:18])=[O:14])=[C:9]([OH:24])[C:8]2[CH2:25][N:26]([C:28](=[O:33])[CH2:29][CH2:30][CH:31]=[CH2:32])[CH2:27][C:7]1=2.C([O-])([O-])=O.[Na+].[Na+].[C:43]1(B(O)O)[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>CC(N(C)C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:2]1([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH:36]=[CH:35][CH:34]=[C:4]([CH2:5][N:6]2[C:11](=[O:12])[C:10]([C:13]([NH:15][CH2:16][C:17]([OH:19])=[O:18])=[O:14])=[C:9]([OH:24])[C:8]3[CH2:25][N:26]([C:28](=[O:33])[CH2:29][CH2:30][CH:31]=[CH2:32])[CH2:27][C:7]2=3)[CH:3]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 86649729HCID 86649729, compound

Product 1

HCID 54747876HCID 54747876, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
115 °C

Procedure

tert-Butyl N-{[1-(3-bromobenzyl)-4-hydroxy-2-oxo-6-pent-4-enoyl-2,5,6,7-tetrahydro-1H-pyrrolo[3,4-b]pyridin-3-yl]carbonyl}glycinate (50 mg, 0.09 mmol, prepared in similar fashion to Intermediate 5 (compound 5-1) was dissolved in DMA (2 mL) in a 10 mL reaction tube of a CEM Corporation Discover 300 Watt microwave reactor. Aqueaous Na2CO3 (2 M, 0.8 mL, 1.6 mmol), phenylboronic acid (20 mg, 0.16 mmol) and bis(triphenylphosphine)palladium(II) chloride (7 mg, 0.009 mmol) were added and the tube was purged with nitrogen, capped and inserted into the microwave reactor and heated at 115° C., for 15 min. The reaction was diluted with EtOAc, washed with 2 M HCl, dried (Na2SO4), filtered and concentrated. The residue was purified on a C-18 reverse phase chromatography column eluted with 0-100% MeCN in water. The desired fractions were concentrated, diluted with EtOAc and washed with 2 M HCl. The organic portion was isolated, dried (Na2SO4), filtered and concentrated affording the title compound, E43-1. HPLC/MS: 501.9 (M+1); Rt=3.22 min.

Workup

  1. customthe tube was purged with nitrogen
  2. customcapped
  3. additionThe reaction was diluted with EtOAc
  4. washwashed with 2 M HCl
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified on a C-18 reverse phase chromatography column
  9. washeluted with 0-100% MeCN in water
  10. concentrationThe desired fractions were concentrated
  11. additiondiluted with EtOAc
  12. washwashed with 2 M HCl
  13. customThe organic portion was isolated
  14. dry with materialdried (Na2SO4)
  15. filtrationfiltered
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-1dfe945688874d849ec0857e466a1418
Source dataset
uspto-grants-2013_02
Patent number
US08372863B2

Reaction notes

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