Pyridine → 1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-3-methyl-4-[(phenylmethyl)oxy]-1H-indazole

HRID 2423085Notes

Reaction equation

HRID 2423085 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[NH:4][N:3]=1.[CH2:19]([O:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][C:28]=1[F:36])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.N1C=CC=CC=1>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[F:36][C:28]1[CH:29]=[C:30]([N:4]2[C:5]3[C:10](=[C:9]([O:11][CH2:12][C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)[CH:8]=[CH:7][CH:6]=3)[C:2]([CH3:1])=[N:3]2)[CH:31]=[CH:32][C:27]=1[O:26][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 27377884-Benzyloxy-3-fluorophenylboronic AcidHCID 178434287HCID 178434287, compound

Product 1

HCID 592729801-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-3-methyl-4-[(phenylmethyl)oxy]-1H-indazoleYield 25.7%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-methyl-4-[(phenylmethyl)oxy]-1H-indazole (D30) (0.952 g, 4 mmol), 4-benzyloxy-3-fluorobenzeneboronic acid (1.97 g, 8.0 mmol), copper (II) acetate (1.09 g, 6.0 mmol), pyridine (0.647 mL, 8.0 mmol) and powdered 4A molecular sieves (4 g) in dichloromethane (25 mL) was stirred in an air atmosphere at room temperature. After 48 hrs, the mixture was filtered through Celite, concentrated, redissolved in ethyl acetate, refiltered and concentrated and then chromatographed (0-50% ethyl acetate in hexane and 0-40% diethyl ether in hexane). A white solid crystallised out from some fractions and this was collected by filtration to give the title compound (D31) (0.45 g).

Workup

  1. filtrationthe mixture was filtered through Celite
  2. concentrationconcentrated
  3. dissolutionredissolved in ethyl acetate
  4. concentrationrefiltered and concentrated
  5. customchromatographed (0-50% ethyl acetate in hexane and 0-40% diethyl ether in hexane)
  6. customA white solid crystallised out from some fractions
  7. filtrationthis was collected by filtration

Sources & evidence

ORD record
ord-79a1df85ff0b494093493feb9a88dd46
Source dataset
uspto-grants-2011_06
Patent number
US07960563B2

Reaction notes

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