Tri-o-tolylphosphine → N-((5-ethoxy-2-fluoro-3-isopropoxyphenyl)(4-(3-(methylsulfonyl)phenyl)-1-trityl-1H-imidazol-2-yl)methyl)-4-(5-methyl-1,2,4-oxadiazol-3-yl)benzenamine

HRID 2104973Notes

Reaction equation

HRID 2104973 reaction equation
Br[C:2]1[N:3]=[C:4]([CH:26]([C:40]2[CH:45]=[C:44]([O:46][CH2:47][CH3:48])[CH:43]=[C:42]([O:49][CH:50]([CH3:52])[CH3:51])[C:41]=2[F:53])[NH:27][C:28]2[CH:33]=[CH:32][C:31]([C:34]3[N:38]=[C:37]([CH3:39])[O:36][N:35]=3)=[CH:30][CH:29]=2)[N:5]([C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=1.[CH3:54][S:55]([C:58]1[CH:59]=[C:60](B(O)O)[CH:61]=[CH:62][CH:63]=1)(=[O:57])=[O:56].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C([O-])(O)=O.[Na+]>COCCOC.O.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:47]([O:46][C:44]1[CH:43]=[C:42]([O:49][CH:50]([CH3:51])[CH3:52])[C:41]([F:53])=[C:40]([CH:26]([C:4]2[N:5]([C:7]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[CH:6]=[C:2]([C:60]3[CH:61]=[CH:62][CH:63]=[C:58]([S:55]([CH3:54])(=[O:57])=[O:56])[CH:59]=3)[N:3]=2)[NH:27][C:28]2[CH:29]=[CH:30][C:31]([C:34]3[N:38]=[C:37]([CH3:39])[O:36][N:35]=3)=[CH:32][CH:33]=2)[CH:45]=1)[CH3:48]

Participants

8

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 516892Sodium BicarbonateHCID 27735423-(Methylsulfonyl)phenylboronic acidHCID 68813809N-((4-bromo-1-trityl-1H-imidazol-2-yl)(5-ethoxy-2-fluoro-3-isopropoxyphenyl)methyl)-4-(5-methyl-1,2,4-oxadiazol-3-yl)benzenamine

Product 1

HCID 68815766N-((5-ethoxy-2-fluoro-3-isopropoxyphenyl)(4-(3-(methylsulfonyl)phenyl)-1-trityl-1H-imidazol-2-yl)methyl)-4-(5-methyl-1,2,4-oxadiazol-3-yl)benzenamineYield 15%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a degassed mixture of Intermediate 66.3 (48 mg, 0.063 mmol), 3-(methylsulfonyl)phenylboronic acid (16 mg, 0.0755 mmol), tri-ortho-tolylphosphine (3.8 mg, 0.0.13 mmol) and NaHCO3 (21.7 mg, 0.258 mmol) in 2 mL DME/H2O (3:1), was added Pd(OAc)2 (1.4 mg, 0.0063 mmol). The mixture was stirred at 80° C. for 1.5 h, then was diluted with EtOAc, washed with H2O and brine, dried (Na2SO4), and concentrated. The crude mixture was purified by flash chromatography (0 to 100% EtOAc/hexanes gradient) to afford 8 mg of Intermediate 66.4 as a colorless solid.

Workup

  1. washwashed with H2O and brine
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customThe crude mixture was purified by flash chromatography (0 to 100% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-4ddc5a2c36254b6f874ad74fb8da157a
Source dataset
uspto-grants-2009_08
Patent number
US07576098B2

Reaction notes

Loading…