Potassium Carbonate → HCID 23582734, compound

HRID 1874182Notes

Reaction equation

HRID 1874182 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]([NH:24][C:25]([NH:27][CH2:28][C:29]([F:32])([F:31])[F:30])=[O:26])([C:16]2[CH:21]=[C:20]([OH:22])[CH:19]=[C:18]([F:23])[CH:17]=2)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:4][C:3]=1[C:33]([F:36])([F:35])[F:34].I[CH2:38][C:39]([F:42])([F:41])[F:40].C([O-])([O-])=O.[K+].[K+]>CS(C)=O.CC#N>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]([NH:24][C:25]([NH:27][CH2:28][C:29]([F:30])([F:31])[F:32])=[O:26])([C:16]2[CH:21]=[C:20]([O:22][CH2:38][C:39]([F:42])([F:41])[F:40])[CH:19]=[C:18]([F:23])[CH:17]=2)[CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[CH:4][C:3]=1[C:33]([F:36])([F:34])[F:35]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 677091,1,1-Trifluoro-2-iodoethaneHCID 23582677HCID 23582677, compound

Product 1

HCID 23582734HCID 23582734, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of (R)-1-(1-(4-fluoro-3-(trifluoromethyl)phenyl)-1-(3-fluoro-5-hydroxyphenyl)-2-phenylethyl)-3-(2,2,2-trifluoroethyl)urea (Example 254, 15 mg, 0.03 mmol) in DMSO (0.15 mL) was added ICH2CF3 (0.02 mL) and K2CO3 (20 mg, 0.2 mmol). The reaction mixture was heated at 70° C. overnight. The reaction was cooled to rt and diluted with CH3CN, filtered and purified by prep HPLC (phenomenex AXIA Luna 75×30 mm, 5μ column eluting with 10-90% ACN/H2O over 10 minutes containing 0.1% TFA; 40 mL/min, monitoring at 220 nm) to give (R)-1-(1-(4-fluoro-3-(trifluoromethyl)phenyl)-1-(3-fluoro-5-(2,2,2-trifluoroethoxy)phenyl)-2-phenylethyl)-3-(2,2,2-trifluoroethyl)urea (Example 255) as white solid (10 mg, yield 58%). LCMS: RT=2.18 min [M+H] 601.2 (Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm). 1H NMR (400 MHz, CDCl3) δ ppm 7.33-7.43 (2H, m), 7.21 (1H, d, J=6.60 Hz), 7.12-7.19 (2H, m), 6.68 (2H, d, J=7.70 Hz), 6.54-6.63 (3H, m), 4.19-4.30 (2H, m), 3.73-3.84 (4H, m).

Workup

  1. temperatureThe reaction was cooled to rt
  2. filtrationfiltered
  3. custompurified by prep HPLC (phenomenex AXIA Luna 75×30 mm, 5μ column eluting with 10-90% ACN/H2O over 10 minutes containing 0.1% TFA; 40 mL/min, monitoring at 220 nm)

Sources & evidence

ORD record
ord-a8ee6a7cdded4385a6f4fdfd3a92913f
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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