Isobutylene oxide → HCID 23582472, compound

HRID 1874230Notes

Reaction equation

HRID 1874230 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-cf538a28c6e547e5ab3c837ced0150cd
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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