2-Dicyclohexylphosphino-2',6'-diisopropoxybiphenyl → HCID 86711962, compound

HRID 1475271Notes

Reaction equation

HRID 1475271 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:28]=[CH:29][CH:30]=1)[CH2:5][N:6]1[C:10]([CH3:11])=[N:9][C:8]([C:12]2[CH:16]=[C:15]([C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)[O:14][N:13]=2)=[N:7]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1.[CH3:64][S:65]([CH:68]1[CH2:73][CH2:72][NH:71][CH2:70][CH2:69]1)(=[O:67])=[O:66].CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:11][C:10]1[N:6]([CH2:5][C:4]2[CH:28]=[CH:29][CH:30]=[C:2]([N:71]3[CH2:72][CH2:73][CH:68]([S:65]([CH3:64])(=[O:67])=[O:66])[CH2:69][CH2:70]3)[CH:3]=2)[N:7]=[C:8]([C:12]2[CH:16]=[C:15]([C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)[O:14][N:13]=2)[N:9]=1

Participants

7

Reactant 4

HCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 222750384-(Methanesulfonyl)piperidineHCID 23676156Sodium t-butoxideHCID 86711961HCID 86711961, compound

Product 1

HCID 86711962HCID 86711962, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3-(1-(3-bromobenzyl)-5-methyl-1H-1,2,4-triazol-3-yl)-5-(4-(trifluoromethoxy)phenyl)isoxazole (100 mg, 0.21 mmol) in toluene (3 mL) were added 2-dicyclohexylphosphino-2′,6′-diisopropoxy-1,1′-biphenyl (10 mg, 0.021 mmol), tris(dibenzylideneacetone)dipalladium (19 mg, 0.021 mmol), 4-(methylsulfonyl)piperidine (70 mg, 0.42 mmol) and sodium tert-butoxide (40 mg, 0.42 mmol). The mixture was heated at 100° C. under inert atmosphere for 5 h. The mixture was concentrated under reduced pressure, diluted with H2O (20 mL) and extracted with EtOAc (3×20 mL). The combined organic layers were washed with H2O (20 mL) and brine (20 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by prep-HPLC (Mobile phase: A=10 mM ammonium bicarbonate/H2O, B=MeCN; Gradient: B=60%-95% in 18 min; Column: XBridge C18, 5 um, 30 mm×150 mm) to afford the title compound as a yellow solid; MS (ES+) C26H26F3N5O4S requires: 561. found: 562 [M+H]+; 1H-NMR (500 MHz, CDCl3) δ 7.88 (d, J=8.8 Hz, 2H), 7.34 (d, J=8.3 Hz, 2H), 7.24 (m, 1H), 7.04 (s, 1H), 6.88 (dd, J=8.2, 2.0 Hz, 1H), 6.78 (m, 1H), 6.72 (d, J=7.6 Hz, 1H), 5.34 (s, 2H), 3.81 (bd, J=12.6 Hz, 2H), 2.96 (m, 1H), 2.86 (s, 3H), 2.77 (m, 2H), 2.49 (s, 3H), 2.23 (bd, J=12.7 Hz, 2H), 1.97-1.91 (m, 2H).

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. additiondiluted with H2O (20 mL)
  3. extractionextracted with EtOAc (3×20 mL)
  4. washThe combined organic layers were washed with H2O (20 mL) and brine (20 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto afford the crude product, which
  9. customwas purified by prep-HPLC (Mobile phase

Sources & evidence

ORD record
ord-c6491aa286d4460a8cde2f7b2fd6d8c3
Source dataset
uspto-grants-2015_04
Patent number
US09018380B2

Reaction notes

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