HCID 23581959, compound → HCID 23581958, compound

HRID 1874205Notes

Reaction equation

HRID 1874205 reaction equation
[NH2:1][C:2](=O)[C:3]([CH3:45])([O:5][C:6]1[CH:7]=[C:8]([C@@:13]([NH:32][C:33](=[O:44])[C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:43])([F:42])[F:41])[CH:35]=2)([C:21]2[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([F:31])[CH:22]=2)[CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:9]=[CH:10][C:11]=1[F:12])[CH3:4]>CN(C=O)C.S(Cl)(Cl)=O.O.CCOC(C)=O>[C:2]([C:3]([O:5][C:6]1[CH:7]=[C:8]([C@@:13]([NH:32][C:33](=[O:44])[C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:42])([F:43])[F:41])[CH:35]=2)([C:21]2[CH:26]=[C:25]([C:27]([F:29])([F:30])[F:28])[CH:24]=[C:23]([F:31])[CH:22]=2)[CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:9]=[CH:10][C:11]=1[F:12])([CH3:45])[CH3:4])#[N:1]

Participants

6

Reactant 1

HCID 23581959HCID 23581959, compound

Product 1

HCID 23581958HCID 23581958, compoundYield 55%

Reagents, catalysts & solvents 4

HCID 24386Thionyl ChlorideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (R)—N-(1-(3-(1-amino-2-methyl-1-oxopropan-2-yloxy)-4-fluorophenyl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-3-(trifluoromethyl)benzamide (Example 274, 30 mg, 0.046 mmol) in DMF (1 mL) at room temperature was added thionyl chloride (3 drops). The reaction mixture was stirred for 40 min and diluted with H2O and EtOAc. The organic layer was washed with H2O, saturated NaHCO3, H2O and saturated NaCl, dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by flash chromatography (silica gel, hexanes/EtOAc) to give pure (R)—N-(1-(3-(2-cyanopropan-2-yloxy)-4-fluorophenyl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-3-(trifluoromethyl)benzamide (Example 275, 16 mg, yield: 55%). LCMS: RT=2.21 min [M+H] 633.3 (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).

Workup

  1. washThe organic layer was washed with H2O, saturated NaHCO3, H2O and saturated NaCl
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by flash chromatography (silica gel, hexanes/EtOAc)

Sources & evidence

ORD record
ord-3c38d2c53858404fae617cfd9deb03aa
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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