Phenol → HCID 57742823, compound

HRID 1806124Notes

Reaction equation

HRID 1806124 reaction equation
[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[Br:10][C:11]1[CH:12]=[C:13]([O:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:14]([NH:17][C:18]2[S:19][CH:20]=[C:21]([CH2:23]Cl)[N:22]=2)=[N:15][CH:16]=1>C1COCC1>[Br:10][C:11]1[CH:12]=[C:13]([O:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:14]([NH:17][C:18]2[S:19][CH:20]=[C:21]([CH2:23][O:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[N:22]=2)=[N:15][CH:16]=1

Participants

5

Reactant 3

HCID 996PhenolHCID 24758Sodium hydrideHCID 57742594HCID 57742594, compound

Product 1

HCID 57742823HCID 57742823, compoundYield 20.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Phenol (0.0356 g, 0.378 mmol) was dissolved in 3 mL THF at ambient temperature. NaH (0.00907 g, 0.378 mmol) was added and the mixture stirred for 30 minutes at ambient temperature. Solid N-(5-Bromo-3-phenoxypyridin-2-yl)-4-(chloromethyl)thiazol-2-amine (0.030 g, 0.0756 mmol) (Example 322) was then added to the reaction and the mixture was stirred at ambient temperature overnight. The reaction was concentrated to dryness, dissolved in CH2Cl2, washed with water, dried over Na2SO4, and concentrated to dryness. The residue was purified by preparative HPLC to give the title compound (0.007 g, 20.4% yield) as the least polar of the two major products. 1H NMR (CDCl3) δ 5.07 (s, 2H), 6.88 (s, 1H), 6.96 (t, J=7.3 Hz, 1H), 7.01 (d, J=8.0 Hz, 2H), 7.07 (d, J=8.8 Hz, 2H), 7.14 (d, J=2.0 Hz, 1H), 7.23-7.31 (m, 3H), 7.43 (t, J=8.0 Hz, 2H), 8.14 (d, J=2.0 Hz, 1H), 8.76 (br s, 1H).

Workup

  1. stirringthe mixture was stirred at ambient temperature overnight
  2. concentrationThe reaction was concentrated to dryness
  3. dissolutiondissolved in CH2Cl2
  4. washwashed with water
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to dryness
  7. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-acdcf06075324452b816874bbf3eaafc
Source dataset
uspto-grants-2013_01
Patent number
US08354540B2

Reaction notes

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