Sodium hydride → methyl 2-(tert-butoxy)-2-(1-(4-fluoro-3-methylbenzyl)-6-methyl-4-(p-tolyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)acetate

HRID 1912537Notes

Reaction equation

HRID 1912537 reaction equation
[C:1]([O:5][CH:6]([C:11]1[C:12]([C:21]2[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=2)=[C:13]2[CH:20]=[CH:19][NH:18][C:14]2=[N:15][C:16]=1[CH3:17])[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:31][C:32]1[CH:37]=[CH:36][C:35]([F:38])=[C:34]([CH3:39])[CH:33]=1>CN(C=O)C.O>[C:1]([O:5][CH:6]([C:11]1[C:12]([C:21]2[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=2)=[C:13]2[CH:20]=[CH:19][N:18]([CH2:31][C:32]3[CH:37]=[CH:36][C:35]([F:38])=[C:34]([CH3:39])[CH:33]=3)[C:14]2=[N:15][C:16]=1[CH3:17])[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 27781354-(Bromomethyl)-1-fluoro-2-methylbenzeneHCID 71209083Methyl 2-(tert-butoxy)-2-(6-methyl-4-(p-tolyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)acetate

Product 1

HCID 71209209methyl 2-(tert-butoxy)-2-(1-(4-fluoro-3-methylbenzyl)-6-methyl-4-(p-tolyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)acetateYield 85%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Methyl 2-(tert-butoxy)-2-(6-methyl-4-(p-tolyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)acetate (15 mg, 0.036 mmol) was dissolved in DMF (2 mL) and cooled to 0° C. Sodium hydride (0.175 mmol, 7 mg, 60% dispersion in oil) was added followed by dropwise addition of 4-(bromomethyl)-1-fluoro-2-methylbenzene. The reaction was stirred at ambient temperature 15 minutes, diluted with water and extracted with ethyl acetate, dried over sodium sulfate and purified by silica-gel chromatography (0-50% ethyl acetate/hexanes gradient elution) to give the title compound as a colorless oil 17 mg, 85%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm=7.52-7.46 (m, 1 H), 7.42-7.35 (m, 1 H), 7.34-7.26 (m, 2 H), 7.16 (d, J=7.2 Hz, 1 H), 7.11 (td, J=2.3, 5.3 Hz, 1 H), 7.02-6.92 (m, 2 H), 6.15 (d, J=3.5 Hz, 1 H), 5.44-5.39 (m, 2 H), 3.77 (s, 3 H), 2.74 (s, 3 H), 2.47 (s, 3 H), 2.26 (d, J=1.4 Hz, 3 H), 1.67 (s, 1 H), 0.93 (s, 9 H); LCMS (m/z) ES+=489 (M+1).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialdried over sodium sulfate
  3. custompurified by silica-gel chromatography (0-50% ethyl acetate/hexanes gradient elution)

Sources & evidence

ORD record
ord-4c5ff2cf757c42bb83910f94dad2eb78
Source dataset
uspto-grants-2013_12
Patent number
US08609653B2

Reaction notes

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