Water → HCID 59815655, compound

HRID 499050Notes

Reaction equation

HRID 499050 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3=[N:13][CH:14]=[C:15]([C:17]([OH:19])=[O:18])[CH:16]=[C:11]3[N:10]=[CH:9]2)=[CH:4][CH:3]=1.[F:20][C:21]([F:32])([F:31])[O:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27]Br)=[CH:25][CH:24]=1.[H-].[Na+].O>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C>[F:20][C:21]([F:31])([F:32])[O:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27][O:1][C:2]2[CH:7]=[CH:6][C:5]([N:8]3[C:12]4=[N:13][CH:14]=[C:15]([C:17]([OH:19])=[O:18])[CH:16]=[C:11]4[N:10]=[CH:9]3)=[CH:4][CH:3]=2)=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 1427851-(Bromomethyl)-4-(trifluoromethoxy)benzeneHCID 59815650HCID 59815650, compound

Product 1

HCID 59815655HCID 59815655, compound

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-(4-hydroxyphenyl)-3H-imidazo[4,5-b]pyridine-6-carboxylic acid (54 mg, 0.21 mmol), tetrabutylammonium iodide (8 mg, 0.021 mmol), 4-(trifluoromethoxy)benzyl bromide (0.13 mL, 0.84 mmol) and sodium hydride (50.4 mg, 1.26 mmol) in DMF (3 mL) was stirred at rt under nitrogen for 4 h. Then, water (3 mL) was added and the mixture washed with EtOAc (10 mL). The aqueous phase was acidified with 6N HCl (aq) and the resulting precipitate isolated by filtration. The EtOAc wash was concentrated in vacuo and the residue dissolved in MeOH and stirred with 6N NaOH (aq) for 2 h prior to acidification (2M HCl (aq) and filtration of product. The combined solids were dried in vacuo to give 3-{4-[(4-(trifluoromethoxy)benzyl)oxy]phenyl}-3H-imidazo[4,5-b]pyridine-6-carboxylic acid. 1H NMR (400 MHz, D6-DMSO) δ 5.26 (s, 2H), 7.26 (d, J=8.9 Hz, 2H), 7.42 (d, J=8.2 Hz, 2H), 7.63 (d, J=8.2 Hz, 2H), 7.82 (d, J=8.9 Hz, 2H), 8.61 (d, J=1.6 Hz, 1H), 8.95 (s, 1H), 8.97 (d, J=1.6 Hz, 1H) and 13.2 (br.s, 1H); MS (ES+): m/z 430 [MH+].

Workup

  1. washthe mixture washed with EtOAc (10 mL)
  2. customthe resulting precipitate isolated by filtration
  3. washThe EtOAc wash
  4. concentrationwas concentrated in vacuo
  5. dissolutionthe residue dissolved in MeOH
  6. stirringstirred with 6N NaOH (aq) for 2 h
  7. filtrationto acidification (2M HCl (aq) and filtration of product
  8. customThe combined solids were dried in vacuo

Sources & evidence

ORD record
ord-e2645eed368b445499d223ea4a3c9175
Source dataset
uspto-grants-2010_08
Patent number
US07767673B2

Reaction notes

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