1,2-Dimethoxyethane → HCID 22480273, compound

HRID 2183195Notes

Reaction equation

HRID 2183195 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[N:15]=[CH:14][N:13](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:12]=3)[CH:9]=2)[N:4](C2CCCCO2)[N:3]=1.[F:41][C:42]([F:53])([F:52])[C:43]1[CH:48]=[CH:47][C:46](B(O)O)=[CH:45][CH:44]=1.COCCOC.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(Cl)Cl>[F:41][C:42]([F:53])([F:52])[C:43]1[CH:48]=[CH:47][C:46]([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:11]4[NH:12][N:13]=[CH:14][N:15]=4)[CH:9]=3)[NH:4][N:3]=2)=[CH:45][CH:44]=1

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 62657Potassium Phosphate, TribasicHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 22479811HCID 22479811, compound

Product 1

HCID 22480273HCID 22480273, compoundYield 11.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
60 °C

Procedure

A mixture of 2-{3-bromo-5-[1-(triphenylmethyl)(1,2,4-triazol-3-yl)]-1H-indazolyl}perhydro-2H-pyran (300 mg, 0.508 mmol), 4-trifluoromethylphenylboronic acid (144 mg, 0.758 mmol, 1.49 equiv.), [1,1′-bis(diphenylphosphino)-ferrocene}dichloropalladium (II) complex with dichloromethane (Aldrich), 41.5 mg (0.0508 mmol, 0.100 equiv.), 2.53 mL of anhydrous DME, and powdered potassium phosphate (K3PO4, 535 mg, 2.52 mmol, 4.96 equiv.) were refluxed for 5 days. The reaction was diluted with CH2Cl2, washed with 2× sat. aq. NaHCO3, dried (Na2SO4), filtered, and concentrated. The crude material was purified by silica gel using 30-40% EtOAc in hexanes. To the purified material was added 5.00 mL of MeOH, and 5.00 mL of 6.0 N aq. HCl. The mixture was heated at 60° C. for 24 h. The reaction mixture was filtered. The solid was further purified by silica gel chromatography using EtOAc affording the title compound (69.3 mg). Further purification by prep HPLC afforded the title compound (18.9 mg, 11.3% yield): 1H NMR (CDCl3/CD3OD) δ 8.74 (s, 1H), 8.41-7.97 (m, 4H), 7.78 (d, 2H), 7.66 (d, 1H); ES-MS (m/z) 330 [M+1]+.

Workup

  1. temperaturewere refluxed for 5 days
  2. washwashed with 2× sat. aq. NaHCO3
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by silica gel using 30-40% EtOAc in hexanes
  7. additionTo the purified material was added 5.00 mL of MeOH, and 5.00 mL of 6.0 N aq. HCl
  8. filtrationThe reaction mixture was filtered
  9. customThe solid was further purified by silica gel chromatography
  10. customFurther purification by prep HPLC

Sources & evidence

ORD record
ord-de6fe71c09cd4bd8b0afe8e77b764989
Source dataset
uspto-grants-2005_05
Patent number
US06897231B2

Reaction notes

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