Potassium Carbonate → HCID 71290101, compound

HRID 1752429Notes

Reaction equation

HRID 1752429 reaction equation
[C:1]([C@@H:4]([NH:6][C:7]1[N:12]=[C:11]([C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=2)[N:10]=[C:9]([C:20]([NH2:22])=[O:21])[CH:8]=1)[CH3:5])(=[O:3])[NH2:2].F[C:24]1[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][CH:25]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[C:1]([C@@H:4]([NH:6][C:7]1[N:12]=[C:11]([C:13]2[CH:18]=[CH:17][C:16]([O:19][C:24]3[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][CH:25]=3)=[CH:15][CH:14]=2)[N:10]=[C:9]([C:20]([NH2:22])=[O:21])[CH:8]=1)[CH3:5])(=[O:3])[NH2:2]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 145174-FluorobenzonitrileHCID 136217478HCID 136217478, compound

Product 1

HCID 71290101HCID 71290101, compoundYield 36.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A 50-mL vial with a screw-top septum was charged with 6-((S)-1-carbamoyl-ethylamino)-2-(4-hydroxy-phenyl)-pyrimidine-4-carboxylic acid amide (100 mg, 0.3 mmol), 4-fluorobenzo-nitrile (40 mg, 0.3 mmol), potassium carbonate (92 mg, 0.7 mmol), and N,N-dimethylformamide (5 mL). The flask was purged with nitrogen and heated to 100° C. for 16 h at which time the reaction was complete. The mixture was then diluted with 20 mL water and extracted with 2×20 mL EtOAc. The combined organic layers were dried over sodium sulfate and concentrated under vacuum. The residue was dissolved in 20% methanol/chloroform and passed through a short plug of silica gel. The fractions containing the desired material were concentrated and suspended in a solution of 20% EtOAc/hexane. The suspension was filtered by vacuum and air was allowed to pass over the cake for one hour. The cake was then transferred to a scintillation vial, powdered, and heated under vacuum for one hour to provide the title compound as a white solid (44 mg, 33%). 1H NMR (DMSO-d6): 8.66-8.59 (m, 2H), 8.35-8.28 (s, 1H), 8.02-7.95 (m, 1H), 7.91-7.84 (m, 2H), 7.79-7.70 (s, 1H), 7.59-7.51 (s, 1H), 7.25-7.15 (m, 4H), 7.14-7.08 (s, 1H), 7.05-6.97 (s, 1H), 4.64-4.49 (m, 1H), 1.43-1.31 (m, 3H). LC/MS: m/z 402[M+H]+.

Workup

  1. customThe flask was purged with nitrogen
  2. additionThe mixture was then diluted with 20 mL water
  3. extractionextracted with 2×20 mL EtOAc
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. concentrationconcentrated under vacuum
  6. dissolutionThe residue was dissolved in 20% methanol/chloroform
  7. additionThe fractions containing the desired material
  8. concentrationwere concentrated
  9. filtrationThe suspension was filtered by vacuum and air
  10. temperatureheated under vacuum for one hour

Sources & evidence

ORD record
ord-12b7e3e205574295833c7ab785f4856f
Source dataset
uspto-grants-2015_10
Patent number
US09163008B2

Reaction notes

Loading…