Cesium fluoride → HCID 56847527, compound

HRID 1467386Notes

Reaction equation

HRID 1467386 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:21]3[C:20]4[CH:19]=[C:18]([O:22][CH:23]([C:35]5[S:36][CH:37]=[CH:38][CH:39]=5)[CH2:24][NH:25]C(=O)OCC[Si](C)(C)C)[C:17]([O:40][CH3:41])=[CH:16][C:15]=4[N:14]=[CH:13][C:12]=3[N:11]([CH3:42])[C:10]2=[O:43])=[C:5]([F:44])[CH:4]=1)#[N:2].[F-].[Cs+]>CS(C)=O>[NH2:25][CH2:24][CH:23]([C:35]1[S:36][CH:37]=[CH:38][CH:39]=1)[O:22][C:18]1[C:17]([O:40][CH3:41])=[CH:16][C:15]2[N:14]=[CH:13][C:12]3[N:11]([CH3:42])[C:10](=[O:43])[N:9]([C:6]4[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][C:5]=4[F:44])[C:21]=3[C:20]=2[CH:19]=1

Participants

4

Reactant 2

HCID 25953Cesium fluorideHCID 86689178HCID 86689178, compound

Product 1

HCID 56847527HCID 56847527, compoundYield 45.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

2-Trimethylsilanylethyl {2-[1-(4-cyano-2-fluorophenyl)-7-methoxy-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinolin-8-yloxy]-2-thiophen-2-ylethyl}carbamate (239 mg, 377 μmol) was dissolved in dimethyl sulfoxide (40 ml) under a dry nitrogen atmosphere. CsF (1.15 g, 7.60 mmol) was subsequently added, and the reaction mixture was stirred at room temperature for 18 h overnight. For work-up, the mixture was decanted off into water (300 ml), and saturated NaHCO3 solution (25 ml) was added. The aqueous phase was extracted three times with ethyl acetate (100 ml each time). The combined organic phases were washed with saturated sodium chloride solution (50 ml), dried over Na2SO4 and filtered. After evaporation of the filtrate, the residue was purified by preparative HPLC (water/1-50% by vol. of acetonitrile in 15 min, flow rate 50 ml/min), giving 4-[8-(2-amino-1-thiophen-2-ylethoxy)-7-methoxy-3-methyl-2-oxo-2,3-dihydroimidazo[4,5-c]quinolin-1-yl]-3-fluorobenzonitrile (83 mg, 170 μmol) as lyophilisate after freeze-drying of the product fractions. MS: 490.1 (M+H+), TLC (HPTLC): Rf=0.50 (methanol/iPr2EtN 99:1, parts by volume).

Workup

  1. customFor work-up, the mixture was decanted off into water (300 ml), and saturated NaHCO3 solution (25 ml)
  2. additionwas added
  3. extractionThe aqueous phase was extracted three times with ethyl acetate (100 ml each time)
  4. washThe combined organic phases were washed with saturated sodium chloride solution (50 ml)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customAfter evaporation of the filtrate
  8. customthe residue was purified by preparative HPLC (water/1-50% by vol. of acetonitrile in 15 min, flow rate 50 ml/min)

Sources & evidence

ORD record
ord-b69fd5833ac94a60acf334a868d702bc
Source dataset
uspto-grants-2015_04
Patent number
US09000153B2

Reaction notes

Loading…