Dimethylformamide → HCID 66850876, compound

HRID 386759Notes

Reaction equation

HRID 386759 reaction equation
Br[C:2]1[CH:37]=[CH:36][CH:35]=[CH:34][C:3]=1[CH2:4][N:5]1[C:10](=[O:11])[C:9]([C:12]([NH:14][CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[O:13])=[C:8]([OH:23])[C:7]2[CH2:24][N:25]([C:27]([C:29]3[N:30]=[CH:31][S:32][CH:33]=3)=[O:28])[CH2:26][C:6]1=2.[CH3:38][N:39](C=O)C>O.[C-]#N.[C-]#N.[Zn+2].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.[Fe+2].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]>[C:38]([C:2]1[CH:37]=[CH:36][CH:35]=[CH:34][C:3]=1[CH2:4][N:5]1[C:10](=[O:11])[C:9]([C:12]([NH:14][CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[O:13])=[C:8]([OH:23])[C:7]2[CH2:24][N:25]([C:27]([C:29]3[N:30]=[CH:31][S:32][CH:33]=3)=[O:28])[CH2:26][C:6]1=2)#[N:39]

Participants

7

Reactant 2

HCID 6228DimethylformamideHCID 66850684HCID 66850684, compound2×

Product 1

HCID 66850876HCID 66850876, compound

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

tert-Butyl N-{[1-(2-bromobenzyl)-4-hydroxy-2-oxo-6-(1,3-thiazol-4-ylcarbonyl)-2,5,6,7-tetrahydro-1H-pyrrolo[3,4-b]pyridin-3-yl]carbonyl}glycinate (0.2 g, 0.34 mmol, prepared in similar fashion to Intermediate 5) was dissolved in DMF (4 mL) and water (0.04 mL). Zn(CN)2 (40 mg, 0.34 mmol), dppf (24.8 mg, 0.045 mmol) and Pd2(dba)3 (17 mg, 0.019 mmol) were added and the flask was evacuated and backfilled with nitrogen 3 times. The mixture was heated at 110° C. overnight. The reaction was cooled and partitioned between EtOAc and 2 M HCl, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel gradient eluted with 0-100% EtOAc in hexane affording the product.

Workup

  1. customthe flask was evacuated
  2. temperatureThe reaction was cooled
  3. custompartitioned between EtOAc and 2 M HCl
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography on silica gel gradient
  8. washeluted with 0-100% EtOAc in hexane affording the product

Sources & evidence

ORD record
ord-46d312056b304c1da738c7a813264ead
Source dataset
uspto-grants-2013_02
Patent number
US08372863B2

Reaction notes

Loading…