Sodium hydride → HCID 136386498, compound

HRID 1821859Notes

Reaction equation

HRID 1821859 reaction equation
[C:1]1([C:7]([C:10]2[NH:18][C:13]3=[CH:14][N:15]=[CH:16][CH:17]=[C:12]3[CH:11]=2)=[N:8][OH:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Br[CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24]>CN(C)C=O>[C:1]1([C:7](=[N:8][O:9][CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C:10]2[NH:18][C:13]3=[CH:14][N:15]=[CH:16][CH:17]=[C:12]3[CH:11]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 136386495HCID 136386495, compound

Product 1

HCID 136386498HCID 136386498, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of phenyl(1H-pyrrolo[2,3-c]pyridin-2-yl)methanone oxime (Example 39) (100 mg, 0.42 mmol) and sodium hydride (17 mg of a 60% in mineral oil, 0.43 mmol) in N,N-dimethylformamide (4 mL) was stirred for 0.5 h. tert-Butyl bromoacetate (60 μL, 0.41 mmol) was added dropwise and the reaction mixture was heated at 60° C. for 3 h. After stirring at room temperature for 12 h, the reaction mixture was quenched with water (10 mL) and extracted with diethyl ether (3×15 mL). The combined organic extracts were washed with water (1×25 mL) and brine (1×25 mL), dried over sodium sulfate and concentrated to an oil. Purification by Biotage chromatography (1-10% methanol in methylene chloride) provided tert-butyl [[[phenyl(1H-pyrrolo[2,3-c]pyridin-2-yl)methylene]amino]oxy]acetate as a tan solid: mp 47-52° C.; 1H NMR (500 MHz, CDCl3) δ 1.46-1.61 (9H, m), 4.63 (0.66H, s), 4.85 (1.33H, s), 6.37 (0.33H, s), 6.53 (0.66H, s), 7.26-7.62 (6H, m), 8.23-8.28 (0.66H, m), 8.84 (0.33H, br s), 8.96 (1H, br s), 9.13 (0.33H, br s), 11.04 (0.66H, br s); ESI MS m/z 352 [C20H21N3O3+H]+; HPLC (Method A) 97.8% (AUC), tR=18.3 and 18.5 min.

Workup

  1. additionwas added dropwise
  2. customthe reaction mixture was quenched with water (10 mL)
  3. extractionextracted with diethyl ether (3×15 mL)
  4. washThe combined organic extracts were washed with water (1×25 mL) and brine (1×25 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated to an oil
  7. customPurification by Biotage chromatography (1-10% methanol in methylene chloride)

Sources & evidence

ORD record
ord-eb2520982e784bf4b673edb37fa69839
Source dataset
uspto-grants-2009_10
Patent number
US07608627B2

Reaction notes

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