Isobutylene oxide → HCID 23582472, compound

HRID 238807Notes

Reaction equation

HRID 238807 reaction equation
[CH:1]1([NH:6][C:7]([NH:9][C@:10]([C:29]2[CH:34]=[CH:33][C:32]([F:35])=[C:31]([OH:36])[CH:30]=2)([C:18]2[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([F:28])[CH:19]=2)[CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.C([O-])([O-])=O.[K+].[K+].[CH3:43][C:44]1([CH3:47])[CH2:46][O:45]1>CN(C=O)C>[CH:1]1([NH:6][C:7]([NH:9][C@:10]([C:29]2[CH:34]=[CH:33][C:32]([F:35])=[C:31]([O:36][CH2:43][C:44]([OH:45])([CH3:47])[CH3:46])[CH:30]=2)([C:18]2[CH:23]=[C:22]([C:24]([F:25])([F:27])[F:26])[CH:21]=[C:20]([F:28])[CH:19]=2)[CH2:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[O:8])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

5

Reactant 3

HCID 11208Isobutylene oxideHCID 11430Potassium CarbonateHCID 59458449HCID 59458449, compound

Product 1

HCID 23582472HCID 23582472, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (R)-1-cyclopentyl-3-(1-(4-fluoro-3-hydroxyphenyl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)urea, prepared as described in Procedure 59, (20 mg, 0.039 mmol) in DMF (0.1 mL) was added K2CO3 (12 mg, 0.086 mmol), followed by 2,2-dimethyloxirane (28 mg, 0.39 mmol). The resulting mixture was stirred at 60° C. for 16 h. The reaction mixture was filtered and the solid was washed with EtOAc. The filtrate was washed with H2O, sat. NaCl and dried over Na2SO4 and filtered. The organic solvent was evaporated under reduced pressure and the residue was 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 afford (R)-1-cyclopentyl-3-(1-(4-fluoro-3-(2-hydroxy-2-methylpropoxy)phenyl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)urea (Example 304) as white lyophillate (11 mg, 56% yield). LCMS: RT=4.066 min [M+H] 577.3 (4 min Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm (retention time, column type, size, solvent, flow rate, gradient). NMR: 400 MHz 1H (CD3OD) ppm 1.27 (d, J=2.20 Hz, 6H), 1.32-1.49 (m, 2H), 1.54-1.76 (m, 4H), 1.81-1.98 (m, 2H), 3.53 (d, J=9.23 Hz, 1H), 3.69 (d, J=9.23 Hz, 1H), 3.78 (d, J=12.74 Hz, 1H), 3.91 (t, J=6.15 Hz, 1H), 4.02 (d, J=12.74 Hz, 1H), 6.63-6.70 (m, 1H), 6.72-6.79 (m, 3H), 7.01 (dd, J=10.99, 8.79 Hz, 1H), 7.09-7.20 (m, 3H), 7.27-7.42 (m, 3H).

Workup

  1. filtrationThe reaction mixture was filtered
  2. washthe solid was washed with EtOAc
  3. washThe filtrate was washed with H2O, sat. NaCl
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customThe organic solvent was evaporated under reduced pressure
  7. customthe residue was 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)

Sources & evidence

ORD record
ord-2c03d8a73b9845ab863a47581ec4501a
Source dataset
uspto-grants-2014_02
Patent number
US08642576B2

Reaction notes

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