Ethyl Acetate → HCID 58442349, compound

HRID 887837Notes

Reaction equation

HRID 887837 reaction equation
[F:1][C:2]([F:23])([F:22])[C@:3]([OH:21])([CH3:20])[CH2:4][NH:5][C:6]([C:8]1[C:13]([NH2:14])=[CH:12][C:11]([C:15]([F:18])([F:17])[F:16])=[C:10](Br)[N:9]=1)=[O:7].[F:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1.CC#N.O.CCOC(C)=O>C1COCC1.C([O-])([O-])=O.[Cs+].[Cs+]>[F:1][C:2]([F:23])([F:22])[C@:3]([OH:21])([CH3:20])[CH2:4][NH:5][C:6]([C:8]1[C:13]([NH2:14])=[CH:12][C:11]([C:15]([F:18])([F:17])[F:16])=[C:10]([C:28]2[CH:29]=[CH:30][C:25]([F:24])=[CH:26][CH:27]=2)[N:9]=1)=[O:7]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 2856454-Fluorophenylboronic acidHCID 18373917Acetonitrile--water (1/1)HCID 58442366HCID 58442366, compound

Product 1

HCID 58442349HCID 58442349, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 10796Cesium carbonateSolvent

Conditions

Temperature
160 °C

Procedure

A mixture comprising 3-amino-6-bromo-5-trifluoromethyl-pyridine-2-carboxylic acid ((S)-3,3,3-trifluoro-2-hydroxy-2-methyl-propyl)-amide (Ex. 3)(100 mg, 0.244 mmol), 4-fluorophenylboronic acid (37.5 mg, 0.268 mmol) and 1,1′ bis(diphenylphosphoshio)ferrocenepalladium dichloride (19.90 mg, 0.024 mmol) was suspended in THF (2 ml) and 1M Cs2CO3 (0.667 ml). The vial was flushed with N2, sealed and heated at 160° C. using microwave radiation for 15 minutes. The mixture was partitioned between EtOAc (50 ml) and water (50 ml). The organic portion was separated and washed with brine (30 ml), dried (MgSO4), filtered through Celite® (filter material) and concentrated in vacuo. The crude residue was dissolved in DMSO (2 ml) and purified by mass directed LCMS using MeCN/Water/0.1% TFA eluent to afford clean product. The product fraction obtained as MeCN/Water/0.1% TFA solution was poured into EtOAc (50 ml) and washed with saturated NaHCO3 (50 ml) to free base the product. The organic portion were combined, dried (MgSO4) and concentrated in vacuo to afford the title compound as a pale orange crystalline solid; 1H NMR (400 MHz, DMSO-d6) δ 8.4 (1H, m), 7.7 (1H, s), 7.49 (2H, m), 7.29 (2H, t), 7.2 (2H, br s), 6.22 (1H, s), 3.68 (1H, m), 3.44 (1H, m), 1.22 (3H, s); LC-MS Rt 4.41 mins[M+H]+ 426 (Method 10minLC_v003).

Workup

  1. customThe vial was flushed with N2
  2. customsealed
  3. customfor 15 minutes
  4. customThe mixture was partitioned between EtOAc (50 ml) and water (50 ml)
  5. customThe organic portion was separated
  6. washwashed with brine (30 ml)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered through Celite® (filter material)
  9. concentrationconcentrated in vacuo
  10. dissolutionThe crude residue was dissolved in DMSO (2 ml)
  11. custompurified by mass
  12. customto afford clean product
  13. washwashed with saturated NaHCO3 (50 ml) to free base the product
  14. dry with materialdried (MgSO4)
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-38106d3f9ab24d59a9a0e5b5ea076181
Source dataset
uspto-grants-2012_08
Patent number
US08247436B2

Reaction notes

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