Hydrochloric Acid → HCID 89495427, compound

HRID 510194Notes

Reaction equation

HRID 510194 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.[OH:9][C:10]([CH3:22])([CH3:21])[C@H:11]([C:13]([NH:15][CH2:16][C:17]([F:20])([F:19])[F:18])=[O:14])[NH2:12].Cl.C(=O)([O-])[O-].[K+].[K+].N1CCC[C@H]1C(O)=O>CS(C)=O.[Cu]I>[Br:8][C:6]1[CH:7]=[C:2]([NH:12][C@@H:11]([C:13]([NH:15][CH2:16][C:17]([F:18])([F:19])[F:20])=[O:14])[C:10]([OH:9])([CH3:21])[CH3:22])[CH:3]=[N:4][CH:5]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 693693,5-DibromopyridineHCID 145742L-ProlineHCID 89495443HCID 89495443, compound

Product 1

HCID 89495427HCID 89495427, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 3,5-dibromopyridine (378 mg, 1.6 mmol), 3-hydroxy-N-(2,2,2-trifluoroethyl)-D-valinamide.HCl I-27b (400 mg, 1.6 mmol), potassium carbonate (882 mg, 6.38 mmol) and L-proline (36.7 mg, 0.319 mmol), in DMSO (5 mL) and degassed with nitrogen was added copper(I) iodide (STREM crushed) (30.4 mg, 0.160 mmol). The reaction was sealed and heated at 80° C. for 64 h. The reaction was quenched into water and extracted with DCM. The organic layer was washed with aq. NaHCO3, dried over sodium sulfate, filtered and concentrated. The residue was purified on silica gel (EtOAc/hexane; 25-100%) to afford the title compound I-27. MS APCI: [M+H]+ m/z=371.1. 1H NMR (600 MHz, DMSO) δ 8.57 (t, J=6.5 Hz, 1H), 8.03 (s, 1H), 7.78 (s, 1H), 7.17 (s, 1H), 6.17 (d, J=6.5 Hz, 1H), 4.77 (s, 1H), 3.85 (m, 2H), 3.80 (d, J=6.5 Hz, 1H), 1.07 (s, 3H), 1.06 (s, 3H).

Workup

  1. customThe reaction was sealed
  2. customThe reaction was quenched into water
  3. extractionextracted with DCM
  4. washThe organic layer was washed with aq. NaHCO3
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified on silica gel (EtOAc/hexane; 25-100%)

Sources & evidence

ORD record
ord-5ed0b6484ed645e1a406fffdbb9c1de2
Source dataset
uspto-grants-2015_08
Patent number
US09096598B2

Reaction notes

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