Sodium hydride → tert-butyl 3-[[[phenyl (1H-pyrrolo[2,3-c]pyridin-2-yl)methylene]amino]oxy]propylcarbamate

HRID 1821873Notes

Reaction equation

HRID 1821873 reaction equation
[NH:1]1[C:5]2=[CH:6][N:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[C:2]1[C:10](=[N:12][OH:13])[CH3:11].[H-].[Na+].[C:16]([NH:23][CH2:24][CH2:25][CH2:26]Cl)([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17]>CN(C)C=O>[C:11]1([C:10](=[N:12][O:13][CH2:26][CH2:25][CH2:24][NH:23][C:16](=[O:17])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[C:2]2[NH:1][C:5]3=[CH:6][N:7]=[CH:8][CH:9]=[C:4]3[CH:3]=2)[CH:11]=[CH:10][CH:2]=[CH:3][CH:4]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 10932310N-Boc-3-ChloropropylamineHCID 1363865051-(1H-pyrrolo[2,3-c]pyridin-2-yl)ethanone oxime

Product 1

HCID 136366032tert-butyl 3-[[[phenyl (1H-pyrrolo[2,3-c]pyridin-2-yl)methylene]amino]oxy]propylcarbamateYield 91.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 1-(1H-pyrrolo[2,3-c]pyridin-2-yl)ethanone oxime (Example 72) (100 mg, 0.42 mmol) and sodium hydride (18 mg of a 60% in mineral oil, 0.45 mmol) in N,N-dimethylformamide (4 mL) was stirred for 0.5 h. N-Boc chloropropylamine (86 mg, 0.44 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 ethyl acetate (3×15 mL). The combined organic extracts were washed with water and brine, dried over sodium sulfate, and concentrated to an oil. Purification by Biotage chromatography (30 to 100% ethyl acetate in hexanes) produced tert-butyl 3-[[[phenyl (1H-pyrrolo[2,3-c]pyridin-2-yl)methylene]amino]oxy]propylcarbamate (76 mg, 46%) as a white solid: mp 52-58° C.; ESI MS m/z 395 [C22H26N4O3+H]+; HPLC (Method A) 98.6% (AUC), tR=19.2 min.

Workup

  1. stirringAfter stirring at room temperature for 12 h
  2. customthe reaction mixture was quenched with water (10 mL)
  3. extractionextracted with ethyl acetate (3×15 mL)
  4. washThe combined organic extracts were washed with water and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated to an oil
  7. customPurification by Biotage chromatography (30 to 100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-1008a0ab6e29402693f4a2fd0d067f37
Source dataset
uspto-grants-2009_10
Patent number
US07608627B2

Reaction notes

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