Sodium hydride → HCID 57330878, compound

HRID 1528681Notes

Reaction equation

HRID 1528681 reaction equation
[NH2:1][C:2]1[C:7]([NH:8][C:9](=[O:12])[O:10][CH3:11])=[CH:6][N:5]=[C:4]([N:13]2[C:21]3[C:16](=[N:17][CH:18]=[CH:19][CH:20]=3)[C:15]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[F:29])=[N:14]2)[N:3]=1.[H-].[Na+].[F:32][C:33]1[CH:40]=[CH:39][CH:38]=[CH:37][C:34]=1[CH2:35]Br>C1COCC1.C(OCC)(=O)C>[NH2:1][C:2]1[C:7]([N:8]([CH2:35][C:34]2[CH:37]=[CH:38][CH:39]=[CH:40][C:33]=2[F:32])[C:9](=[O:12])[O:10][CH3:11])=[CH:6][N:5]=[C:4]([N:13]2[C:21]3[C:16](=[N:17][CH:18]=[CH:19][CH:20]=3)[C:15]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[F:29])=[N:14]2)[N:3]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 67968alpha-Bromo-o-fluorotolueneHCID 69257509HCID 69257509, compound

Product 1

HCID 57330878HCID 57330878, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

47 mg (0.12 mmol) of the compound from example 15A were initially charged in 3 ml of THF, and the mixture was cooled to 0° C. Subsequently, 5 mg (0.12 mmol) of sodium hydride (60% in mineral oil) were added and the mixture was stirred at 0° C. for a further 30 min. Thereafter, 14 μl (0.12 mmol) of 2-fluorobenzyl bromide were added dropwise, and the mixture was stirred at RT overnight. The reaction mixture was diluted with ethyl acetate and the organic phase was washed twice with saturated aqueous sodium bicarbonate solution. The organic phase was then dried over magnesium sulfate, filtered and concentrated. The residue was purified by means of preparative HPLC (acetonitrile:water (+0.1% formic acid) gradient). The crude product obtained in this manner was purified by means of preparative thin-layer chromatography (mobile phase: dichloromethane-methanol 20:1). This gave 8 mg of the target compound (13% of theory).

Workup

  1. stirringthe mixture was stirred at RT overnight
  2. washthe organic phase was washed twice with saturated aqueous sodium bicarbonate solution
  3. dry with materialThe organic phase was then dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by means of preparative HPLC (acetonitrile:water (+0.1% formic acid) gradient)

Sources & evidence

ORD record
ord-1f020135a56349aabd4b45e5b15c9f0e
Source dataset
uspto-grants-2015_07
Patent number
US09090609B2

Reaction notes

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