Potassium Phosphate, Tribasic → HCID 118195282, compound

HRID 923945Notes

Reaction equation

HRID 923945 reaction equation
Br[C:2]1[CH:21]=[CH:20][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][CH:10]=2)=[O:7])=[CH:4][C:3]=1[C:22]1[CH:23]=[N:24][CH:25]=[N:26][CH:27]=1.[O:28]1[CH2:32][CH2:31][NH:30][C:29]1=[O:33].[O-]P([O-])([O-])=O.[K+].[K+].[K+].CN[C@@H]1CCCC[C@H]1NC>O1CCOCC1.CCOC(C)=O.[Cu](I)I>[O:33]=[C:29]1[N:30]([C:2]2[CH:21]=[CH:20][C:5]([C:6]([NH:8][C:9]3[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][CH:10]=3)=[O:7])=[CH:4][C:3]=2[C:22]2[CH:23]=[N:24][CH:25]=[N:26][CH:27]=2)[CH2:31][CH2:32][O:28]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 739492-OxazolidinoneHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 89906673HCID 89906673, compound

Product 1

HCID 118195282HCID 118195282, compound

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

4-Bromo-3-(pyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide (Stage 117.1, 100 mg, 0.228 mmol), oxazolidin-2-one (79 mg, 0.913 mmol), copper iodide (4.35 mg, 0.023 mmol) and finely ground K3PO4 (143 mg, 0.672 mmol) were added to a MW vial. The vial was sealed, evacuated/purged with argon and a solution of trans-N,N′-dimethylcyclohexane-1,2-diamine (7.20 μL, 0.046 mmol) in dioxane (456 μL) was added. The RM was then stirred at 110° C. for 20 hr. The RM was diluted with EtOAc (5 mL), washed with 1M HCl (20 mL) and extracted with EtOAc. The combined extracts were sequentially washed with NH4OH (32%)/NH4Cl (sat.) 1:5 (10 mL), and brine (10 mL), dried over Na2SO4, and the mixture was evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography (RediSep® Silica gel column, 12 g, cyclohexane/EtOAc-EtOH+0.1% NH4OH (9:1), from 20% to 90% EtOAc-EtOH+0.1% NH4OH (9:1)). Second purification was performed by preparative HPLC (Condition 13, from 5% to 100% in 14 min) afforded the title compound as a brown solid. UPLC-MS (condition 1) tR=2.13 min, m/z=445.1 [M+H]+, m/z=443.2 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 4.03-4.21 (m, 2H) 4.32-4.49 (m, 2H) 7.39 (d, J=8.31 Hz, 2H) 7.72-7.83 (m, 1H) 7.84-7.93 (m, 2H) 8.06-8.17 (m, 2H) 8.96 (s, 2H) 9.22 (s, 1H) 10.49 (s, 1H).

Workup

  1. customThe vial was sealed
  2. customevacuated/purged with argon
  3. washwashed with 1M HCl (20 mL)
  4. extractionextracted with EtOAc
  5. washThe combined extracts were sequentially washed with NH4OH (32%)/NH4Cl (sat.) 1:5 (10 mL), and brine (10 mL)
  6. dry with materialdried over Na2SO4
  7. customthe mixture was evaporated to dryness under reduced pressure
  8. customThe crude product was purified by flash chromatography (RediSep® Silica gel column, 12 g, cyclohexane/EtOAc-EtOH+0.1% NH4OH (9:1), from 20% to 90% EtOAc-EtOH+0.1% NH4OH (9:1))
  9. customSecond purification
  10. customwas performed by preparative HPLC (Condition 13, from 5% to 100% in 14 min)

Sources & evidence

ORD record
ord-21e909b140bf4fb2b5722413cb1e354b
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

Loading…